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  • Mice  (2,230)
  • Nature Publishing Group (NPG)  (2,147)
  • Springer  (83)
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  • 1
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    Springer
    Development genes and evolution 197 (1988), S. 63-65 
    ISSN: 1432-041X
    Keywords: Chimeras ; In situ hybridization ; Mice ; Transgenic
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary We describe the construction of aggregation chimeras between normal and transgenic embryos containing multiple copies of mouse β-globin genes. The transgenic component of the chimeras is then detected in tissue sections by a DNA-DNA in situ hybridization technique, using a biotinylated DNA β-globin probe and an avidin-linked alkaline phosphatase detection system. The general advantages of transgenic markers for chimeras are discussed.
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  • 2
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    Cellular and molecular life sciences 41 (1985), S. 1455-1456 
    ISSN: 1420-9071
    Keywords: Mice ; uterus ; vagina ; sex steroids ; glycogen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Estradiol dipropionate induces an increase (3-fold) in the uterine glycogen content and a decrease (4-fold) in the vaginal glycogen content of Parkes (P) mice. Progesterone antagonizes this estradiol dipropionate-induced response in both the uterine and vaginal tissue. The degree of this antagonism is more pronounced in the uterus than in the vagina.
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  • 3
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    Cellular and molecular life sciences 44 (1988), S. 253-254 
    ISSN: 1420-9071
    Keywords: Mice ; heritable mutations ; sperm enzyme activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Male mice were injected i.p. with 2.5 mg/kg mitomycin C, 100 mg/kg ethyl nitrosourea or saline and mated with untreated virgin females five weeks later. Sperm from 64 of the F1 male progeny were analyzed histochemically for acrosin, succinic dehydrogenase and alpha-glycerophosphate dehydrogenase activity. The frequency of F1 males with sub-normal sperm enzyme activity was significantly higher among progeny from treated males than in controls. These results show that analysis of sperm enzyme activity in F1 males is a practical method for detection of transmitted mutations induced in a treated parent.
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  • 4
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    Journal of comparative physiology 174 (1994), S. 13-26 
    ISSN: 1432-1351
    Keywords: Insects ; Antennae ; Toads ; Mice ; Mantids ; Spiders
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract 1. Interactions of cockroaches with 4 different predator species were recorded by videography. Some predators, especially spiders, struck from relatively short distances and usually contacted a cockroach prior to initiation of escape (Table 1, Fig. 3). This touch frequently occurred on an antenna. Cockroaches turned away from the side on which an antenna was touched. 2. We then measured the success of escape from predators for cockroaches with either cerci or antennae ablated. Only antennal removal caused a significant decrease in the success of escape from spiders (Fig. 5). 3. With controlled stimuli, cockroaches responded reliably to abrupt touch of antennae, legs or body (Fig. 6). Responses resembled wind-elicited escape: they consisted of a short latency turn (away from the stimulus) followed by running (Figs. 7, 8). However, lesions show that touchevoked escape does not depend on the giant interneuron system (Table 2). 4. Following section of one cervical connective, cockroaches continued to respond to touching either antenna, but often turned inappropriately toward, rather than away from, stimuli applied to the antenna contralateral to the severed connective (Table 3, Fig. 10). 5. For certain types of predators touch may be a primary cue by which cockroaches detect predatory attack. Descending somatosensory pathways for escape are distinct from the GI system.
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  • 5
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    Neuroscience and behavioral physiology 30 (2000), S. 195-200 
    ISSN: 1573-899X
    Keywords: Mice ; dominance ; subordinacy ; stress ; aggression ; locomotor activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The behavior of individaals and their responses to external stimuli are controlled by the microsocial environment, which for most mammals is associated with dominant-subordinate relationships. Physiological and behavioral differences between dominant and subordinate individuals may be ‘primary’ (genetically determined) or ‘secondary’ (due to position in the group's hierarchical structure). A series of experiments was conducted to investigate the physiological (pain response threshold), immunological (thymus, spleen weights, primary immune response), and behavioral (motor activity, behavior in a shuttle box test) characteristics of dominant and subordinate individuals in groups of three laboratory mice formed on the basis of linear hierarchy. Assessment of the effects of group conditions was made using a conditioned reflex location preference test. The results showed: 1) there are no statistically significant differences in physiological and behavioral (except for motor activity) parameters between dominant and subordinate mice; 2) co-housing of dominant and subordinate individuals in groups with stable hierarchical relationships was not aversive for them.
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  • 6
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    Journal of biomedical science 2 (1995), S. 146-153 
    ISSN: 1423-0127
    Keywords: Transgene ; Mice ; Embryogenesis ; HIV ; Toxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The likelihood that expression of a foreign gene in a mammalian cell is deleterious to viability is confronted whenever novel transgenic animals are made. A pathological response to transgene expression is even desired in transgenic mouse models of human disease. The derivation of HIV-transgenic mice in our laboratory using multiple recombinant forms of an HIV provirus has resulted in mixed success best explained by the variable toxicity of the different transgenes. Employing a standardized approach to pronuclear injections, experimental variation amongst recombinant HIV transgenes was documented in terms of the percentage of pregnancies following embryo transfer into pseudopregnant mice and the percentage of transplanted embryos leading to term births in these pregnant females (giving rise to an index of birth success, SI). Results compiled over 5 years suggested that the SI reflected transgene toxicity, in this case of HIV gene products early in embryogenesis. These observations have guided the design of productive transgenes for mouse models of HIV-related diseases and may be generally applicable in transgenesis.
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  • 7
    ISSN: 1423-0127
    Keywords: Enterovirus type 71 ; Experimental infection ; Mice ; Neutralizing antibody ; Vaccine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Experimental infection with enterovirus type 71 (EV71) induced death in neonatal mice in an age- and dose-dependent manner. The mortality rate was 100% following intraperitoneal inoculation 1-day-old ICR mice and this gradually decreased as the age at the time of inoculation increased (60% in 3-day-old mice and no deaths occurred in mice older than 6 days of age). A lethal dose greater than 108 PFU was necessary. Lethargy, failure to gain weight, rear limb tremors and paralysis were observed in the infected mice before death. EV71 was isolated from various tissues of the dead mice. Using a reverse transcription polymerase chain reaction technique with a specific primer pair, a 332-bp product was detected in the tissues that produced a culture positive for EV71. Protection against EV71 challenge in neonatal mice was demonstrated following passive transfer of serum from actively immunized adult mice 1 day after inoculation with the virus. Pups from hyperimmune dams were resistant to EV71 challenge. Additionally, maternal immunization with a formalin-inactivated whole-virus vaccine prolonged the survival of pups after EV71 lethal challenge.
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  • 8
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    Calcified tissue international 27 (1979), S. 19-26 
    ISSN: 1432-0827
    Keywords: Bone diseases ; Familial hypophosphatemia ; Magnesium ; Mice ; Phosphorus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary A new genetic mutant in mice,Hyp, has been proposed as a model for the human disease X-linked hypophosphatemia (the most common form of vitamin D-resistant rickets). The gene is X-linked, dominant, and produces reduced renal tubular reabsorption of phosphate, hypophosphatemia, and dwarfism. Our goal was to evaluate the skeletal changes histologically and to measure chemically the prominant blood and bone minerals to judge the suitability of this mutant as a model for the human disease. Thirteen-week-old hemizygousHyp male mice were compared with their normal littermate controls. TheHyp mice were hypocalcemic, hypophosphatemic, hypermagnesemic, and had elevated plasma alkaline phosphatase. The femur ash weighed less than half the normal ash weight but had a normal Ca:P ratio. The ash composition was high in %Na and K but low in %Mg. The mandibular incisor ash was also low in %Mg. Histologically the femur showed wide osteoid borders and wide epiphyseal plate. Microradiography revealed reduced bone density and enlarged osteocyte lacunae. Skeletal muscle samples, although smaller in theHyp mice, showed no striking alternations in inorganic or total phosphate content, dry weight (as % wet weight), or extracellular fluid space. TheHyp gene in mice seems to produce a condition similar to that of X-linked hypophosphatemia in humans.
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  • 9
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    Theoretical and applied genetics 71 (1985), S. 44-51 
    ISSN: 1432-2242
    Keywords: Heterosis ; Mice ; Selection ; Growth
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary To examine the effect of selection on levels of heterosis, crosses were made between three groups of six lines of mice, one group unselected (controls) and the other two selected for high (large lines) and low (small lines) 6-week body weight, respectively. The coefficient of inbreeding of each line was about 0.60. Each line was crossed reciprocally to one line from each of the parental groups, as well as producing purebred progeny. Heterosis for 3-week weight, 6-week weight and 3–6 week gain averaged 0.0%, 2.4% and 4.2%, respectively, and was higher for males than for females. Heterosis was more extensive in crosses involving large or control lines than in crosses with small lines. There was no detectable heterosis in several measures of developmental rate, such as age at vaginal opening. Food conversion efficiency and carcass composition were measured on a sample of the animals. Food consumption, gonadal fat pad weight, and hindquarters weight, each expressed as a proportion of body weight, exhibited −4.0%, 5.6%, and 2.3% heterosis, respectively.
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  • 10
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    Theoretical and applied genetics 76 (1988), S. 148-156 
    ISSN: 1432-2242
    Keywords: Growth curve ; Genetic parameters ; Heritability ; Mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Data from 1,919 outbred ICR mice were used to examine the potential usefulness of growth curve parameters as selection criteria for altering the relationship between body weight and age. A logistic growth function was used to model growth through 12 weeks of age. Estimates of asymptotic weight (A), maximum growth rate (r) and age at point of inflection (t*) were obtained by nonlinear least-squares. A log transformation was also used to stabilize residual variance. Phenotypic and genetic parameters were estimated for the estimated growth curve parameters and for body weights at 2, 3, 4.5, 6, 8 and 12 weeks of age. Heritabilities of estimated growth curve parameters (obtained with and without a log transformation, respectively) were: A (0.28±0.07, 0.28±0.07), r (0.35±0.07, 0.53±0.09) and t* (0.41±0.08, 0.44±0.08). Estimated genetic correlations suggest that t* may be useful in selecting for rapid early growth without increasing mature weight.
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  • 11
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    Calcified tissue international 28 (1979), S. 259-262 
    ISSN: 1432-0827
    Keywords: C-type virus particles ; Bone tissue ; Mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The proximal tibial metaphysis of apparently healthy strain 101 mice, 3–4 weeks old, and (C3H×101)F1 hybrids, 3–48 weeks old, was studied by electron microscopy. Budding, immature, and mature C-type virus particles were found within trabecular bone tissue of 3 of 8 strain 101 and 4 of 12 (C3H×101)F1 mice. The particles were most common in lacunae of aging osteocytes and were only occasionally associated with osteoblasts. Although the morphology of budding and immature particles appeared to be identical with that of typical C-type viruses, most of the mature forms of particles showed atypical structure and size. The electron-dense core was very large and not clearly defined, measuring approximately 70–130 nm in diameter. This diffuse core sometimes completely filled the space within the envelope of the particles. The diameters of the pleomorphic mature C-type particles ranged from approximately 90 to 150 nm. The possible association between the production of pleomorphic C-type virus particles by bone cells and spontaneous osteomagenesis in 101 and (C3H × 101)F1 mice is discussed.
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  • 12
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    Calcified tissue international 36 (1984), S. 662-667 
    ISSN: 1432-0827
    Keywords: Vitamin D ; Hyp ; X-linked hypophosphatemia ; Metabolic bone disease ; Mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary Hyp mice are a model for human X-linked hypophosphatemia (vitamin D-resistant rickets.) To determine whether an abnormality of vitamin D metabolism exists in this disease, the profiles of the metabolites of vitamin D were determined in normal andHyp mouse plasma.Hyp and normal mice were fed a vitamin D-deficient diet and received 1,23H-vitamin D3 at 16 Ci/mmol by stomach tube at 5 ng/g body weight (0.21 µCi/g b.w.) on alternate days for 14 days. The dose of vitamin D given maintained near normal plasma 25-OH-vitamin D. Thus the mice were in a vitamin D-replete state with all metabolite pools labeled with3H. Plasma was collected from 4 normal and 4Hyp mice. The plasma was extracted, and the extracts were chromatographed separately for each mouse on an LH-20 column. Each major peak of radioactivity was rechromatographed using high performance liquid chromatography on a Zorbax-Sil column using solvent systems known to resolve several vitamin D metabolites. Twenty-one radioactive peaks were identified. The disintegrations per minute of3H in each peak were quantified and converted to plasma concentration using the known specific activity of the administered vitamin D. The 25-OH-vitamin D accounted for 55% of the circulating radioactivity, and 24,25-(OH)2-vitamin D accounted for 22%. The plasma levels of 24,25-(OH)2-vitamin D were similar to levels previously reported by us using protein binding assays. No peaks of radioactivity were missing in the plasma extracts of theHyp mice. Also there was no evidence that plasma 24,25-(OH)2-vitamin D was elevated in theHyp mice.
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  • 13
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    Theoretical and applied genetics 62 (1982), S. 281-287 
    ISSN: 1432-2242
    Keywords: Growth ; Alkaline phosphatase ; Selection ; Correlated responses ; Mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The effectiveness of two way selection for plasma alkaline phosphatase (ALP) was investigated in order to determine its influences on growth traits through thirteen generations. The responses of the two lines selected for high (HP) and low (LP) ALP at 45 days of age were compared to that of the mice selected for large (L) and small (SM) body size. The selection responses of plasma ALP were very effective for both HP and LP lines, with average responses per generation calculated from linear regressions of 0.227±0.037 and −0.088±0.022 respectively. The final levels of ALP in HP and LP were 5.54±0.71 and 1.27±0.20 in the thirtheenth generation, while the SM, L and base population had levels of 3.49±0.08, 0.86±0.55 and 2.77±0.56 respectively. The body weight at 45 days of age in LP (31.4±1.4 g) as a correlated response was significantly higher than HP (23.4±1.8 g) at generation 10. The correlated response of milk yield, measured by weight gain up to 12 days of age, was significantly greater in the LP line than in HP, but the correlated response of gains after weaning was not so different as the response of milk yield. The response of litter size and weight in LP showed significant higher levels than that of HP, but pups' birth weight did not differ between LP and HP. It is suggested that the correlated response of milk yield contributed more to the divergence of body size between HP and LP than the gain after weaning. Realized heritabilities of ALP were 0.335±0.059 (HP) and 0.279±0.051 (LP). Realized genetic correlations between ALP and 45 days' body weight were −0.27±0.13 (HP with SM) and −0.52±0.19 (LP with L). Realized genetic correlations between ALP and milk yield were −0.95±0.03 (HP) and −0.37±0.29 (LP). Correlations between ALP and postweaning gains were fairly low.
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  • 14
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    Theoretical and applied genetics 63 (1982), S. 145-150 
    ISSN: 1432-2242
    Keywords: Mice ; Selection ; Growth rate ; ad libitum feeding ; Restricted feeding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Selection for post-weaning weight gain in mice from 21 to 42 days, on either a full or restricted feeding level during this period was carried out for seven generations. Control lines were maintained for each feeding level. The rate of selection response was higher on full feeding due to a higher heritability and a larger phenotypic variance. Realised heritabilities of 0.29±0.05 and 0.19±0.04 for selection on full and restricted feeding respectively, were in close agreement with base population estimates. Selection on full feeding led to positive correlated responses in 21 day weight, 42 day weight, food intake and efficiency between 21 and 42 days, and 42 day tail length, but with little change in reproductive performance. Correlated responses to selection on restricted feeding were reduced 21 day weight, but an increase in 42 day weight and increased efficiency from 21 to 42 days. However, overall reproductive performance fell.
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  • 15
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    Theoretical and applied genetics 67 (1984), S. 479-484 
    ISSN: 1432-2242
    Keywords: Heterosis ; Lifetime performance ; Mice ; Male and female ; Mate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Six straightbred lines of mice, some of their F1 crosses and a synthetic line were used to evaluate male and female contributions to heterosis in lifetime performance measured on females. Females from each straightbred line or F1 crosses were pair-mated randomly at day 42 with either a male of the corresponding genetic group or from a synthetic line, and pairs were maintained for 155 days (lifetime). Each mother was allowed to rear all young born alive until day 18 when the young were discarded. Data were analyzed using a model in which the group mean of lifetime performance was expressed as the sum of (additive direct) genetic and environmental effects for each of the male and female genetic groups used for mating. Comparison of group means for lifetime performance revealed that estimates of F1 heterosis due to male and female averaged 10 and 9% for number of parturitions during lifetime, 7 and 28% for total number of young born alive, 6 and 31% for total body weight of young born alive, 8 and 33% for total number of young raised to day 18, 9 and 43% for total body weight of young raised to weaning, and 8 and 8% for days from first mating to last parturition. The male's contribution to heterosis in lifetime performance was smaller than female's contribution for productive traits (total number of young born alive and at day 18, and total body weight of young born alive and at day 18), and was nearly equal in reproductive traits (number of parturitions during lifetime and days from first mating to last parturition).
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  • 16
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    Theoretical and applied genetics 70 (1985), S. 72-79 
    ISSN: 1432-2242
    Keywords: Mice ; Selection experiments ; Plateau ; Fertility
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary A long-term experiment for increasing the traits first day litter size (LS1) and litter weight (LW1) was conducted with two populations for 33 generations. The selection plateau was reached in population DU-C (selection and estrus synchronization (h2 = 0.02±0.01); in population DU-K (selection) the plateau (h2 = 0.05±0.2) was nearly reached. Selection progress per generation was in LS1 b = 0.11±0.02; b = 0.12±0.04 (1st to 18th generation DU-K, DU-C) and b = 0.10±0.03; b = 0.07±0.05 (19th to 33rd generation, DU-K, DU-C) in LW1 b = 0.16±0.04 g; 0.19±0.07 g (DU-K, DU-C) b = 0.20±0.09 g; 0.001±0.09 g (DU-K, DU-C). Reverse and relaxe selection as well as systematic inbreeding was applied for 10 generations. Reverse selection yielded h2 = 0.28±0.11 (R-DU-K) and h2 = 0.17±0.05 (R-DU-C) and showed that there was still additive genetic variance. Relaxe selection did not cause alterations in the selection parameters, whereas inbreeding lead to inbred depressions (b = LS1 = −0.42±0.15; −0.45±0.12; b = LW1 = −1.13±0.20; −0.82±0.18 I-DU-K, I-DU-C). The plateau was based upon the heterozygote advantage. Several methods for overcoming the plateau were applied. A new selective useful variance could be created by crossing the plateau populations (h2 = 0.14±0.04). A short-term progress in overcoming the plateau (1st to 3rd generation) could be obtained by litter size standardization (LS = 388). Tandem selection (selection for body weight — BW42) as well as crossing of inbred strains were not suitable for overcoming the selection plateau. Altering the environmental conditions as a possibility for overcoming the plateau has been discussed.
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  • 17
    ISSN: 1432-2242
    Keywords: Transgene ; Mice ; Growth ; Reproduction ; Selection response
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Frequencies of mice with the rat growth hormone (rGH) transgene were examined in lines derived from two genetic bases (P/W and P/C). The genetic bases were developed from males (P) with the rGH transgene, mated with non-transgenic females of different origin: a line previously selected for large body size (W) and a corresponding unselected control line (C). They were maintained for six generations under random mating with or without selection for increased 42-day body weight. The frequencies of P/W and P/C males with the rGH transgene wer 0.075 and 0.300, respectively at generation 0 of the genetic bases. They were significantly (P〈0.05) lower than the expected frequency (about 0.5). At generation 6, the frequencies had decreased further both in selected and unselected lines (ranging from 0.025 to 0.125). Decreased frequencies of mice with the transgene were confirmed in a separate experiment testing segregation of the transgene. The reasons for these decreases are not clear. The results suggest that transgenes need to be monitored when transgenic animals are mated with animals of different origin.
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  • 18
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    Theoretical and applied genetics 83 (1992), S. 973-980 
    ISSN: 1432-2242
    Keywords: Mice ; Fat ; Selection index ; Heritability ; Genetic correlation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Replicated within full-sib family restricted index selection was conducted for eight generations in mice for high or low epididymal fat pad weight (EF) holding body weight (BW) constant. Pooled realized heritability estimates of index units based on high, low and divergent selection were 0.42±0.20, 0.44±0.19 and 0.42± 0.05, respectively, which were not different from the base population estimate of 0.33±0.10. Realized responses per generation pooled across replicates in the high-fat restricted index lines were in the expected directions for EF (17.5±7.2 mg; P〈0.05) and BW (0.03±0.58 g; P〉0.05), but responses in the low-fat restricted index lines were discrepant for EF (0.3±5.1 mg; P〉0.05) and BW (0.38±0.01 g; P〈0.01). Consequently, the realized responses in component traits were decidedly asymmetric (P〈0.05). A technique for estimating realized genetic parameters from index selection lines gave realized heritabilities for BW and EF of 0.68±0.04 and 0.45±0.05, respectively, and a realized genetic correlation between BW and EF of 0.93±0.01 compared with base population estimates of 0.43±0.08, 0.49±0.10 and 0.78±0.05, respectively. Possible explanations for the disparity between observed and expected responses in the low-fat restricted index lines include genetic drift, poor estimates of base population parameters, changes in genetic parameters with selection, linkage disequilibrium resulting from selection and asymmetric realized relative index weights.
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  • 19
    ISSN: 1432-2242
    Keywords: Growth hormone ; Mice ; Transgene ; Growth
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract The effects of a high-growth genetic background on the growth of mice hemizygous for one of two growth hormone transgenes were examined. Male mice hemizygous for wild-type (W) and dwarf mutant (M) bovine growth hormone (bGH) transgenes were crossed with females of a high-growth selected (S) and control (C) line as follows: W x S, W x C, M x S and M x C. Body weights of progeny were recorded weekly from 2 to 10 weeks of age. F1 progeny were classified as carriers (P) or non-carriers (N) of the transgene by assaying tail DNA for bGH using the polymerase chain reaction and agarose gel electrophoresis. A deficiency in the number of f1 progeny carrying the W (P〈0.05) and M (P〈0.01) bGH transgene was most likely due to differential prenatal and early postnatal mortality. Bodyweight means of wild-type transgenic mice were larger (P 〈 0.05) than those of non-transgenic littermates by 3 weeks of age in a C background in contrast to 5 weeks in S. The wild-type bGH transgene increased adult body weights more in the C (155%) than in the S (136%) background, indicating transgene expression by selection background interaction (P 〈 0.05). However, the growth response to the wild-type transgene in the S background was still large. The dwarf mutant transgene had a greater effect on growth reduction in the S (70%) than in the C (84%) background, thus causing transgene expression by selection background interaction (P 〈 0.05). Gender by wild-type transgene effect interactions (P 〈 0.001) for adult body weight were caused by the transgene reducing the gender difference for body weight in C and eliminating it in S. The dwarf mutant caused a larger negative effect on growth in males than in females, resulting in a gender by dwarf mutant transgene interaction (P 〈 0.001) for adult body weights. Results indicate that the effect of a GH transgene on growth can be affected both by a high-growth genetic background and the gender of progeny.
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  • 20
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    Theoretical and applied genetics 73 (1987), S. 926-931 
    ISSN: 1432-2242
    Keywords: Selection ; Feeding levels ; Growth ; Body composition ; Mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary Two lines of mice were selected for high post-weaning weight gain (3 to 6 weeks) adjusted for 3 week weight. One line (F) was grown on freely available food and the other (S) on a feeding scale set at the same level for all mice. Food intake of the S line averaged 80% of the F line. The realised heritabilities after 6 generations of selection were 0.38±0.06 and 0.33±0.07 for the F and S lines, respectively. In generation 7, mice from the F and S lines and from an unselected control line (C) were compared on both free and set levels of feeding from 3 weeks to 9 weeks of age. Measurements taken were growth rate, appetite, food conversion efficiency (weight gain/food intake) and body composition (fat, protein, ash, water). The F and S lines grew more rapidly and efficiently than the C line on both levels of feeding, each line performing best on the level of feeding on which it was selected. The average genetic correlation between growth rates of the same line on the two feeding levels was 0.54±0.10. The F line grew 19% faster and was 9% more efficient than the S line on free feeding but the S line grew 15% faster and was 15% more efficient than the F line on set feeding. Relative to the C line, food intake per day on free feeding was 4% higher in the F line and 6% lower in the S line. There was no difference between the lines in food intake/g body weight. The rate of deposition of all body components increased in both selection lines. In the F, S and C lines respectively, efficiencies of gains in body components (102x gain/food) were 1.79, 1.31 and 1.06 for fat, 1.53, 1.63 and 1.22 for protein and 5.88, 6.45 and 4.98 for protein + water. Apparently energy lost as heat was reduced in both the F and S lines. The partitioning of energy retained was altered in favour of more fat in the F line and more protein in the S line.
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  • 21
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    Theoretical and applied genetics 79 (1990), S. 131-136 
    ISSN: 1432-2242
    Keywords: Selection response ; Metabolic rate ; Inheritance of activity ; Mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary The aim of this study was to examine the differences in physical activity and their contribution to differences in energy utilization in mice, selected either high or low for food intake, adjusted for body weight, which show correlated responses in lean content and metabolic rate. Simultaneous measurements of fasting metabolic rate and activity were made in lines of mice selected at either: a young age, 4-to 6-week food intake corrected for 4-week body weight; or an older age, 8- to 10-week food intake corrected for mean weight at 8 and 10 weeks of age. Correlated response in metabolic rate was found to have been accompanied by changes in locomotor activity near the ages at selection in both sets of lines. Activity, however, accounted for only a small proportion of variation in fasting heat production, generally less than 5%, although a highly positive correlation (r=0.63) between the two traits was found. It was concluded that selection for food intake adjusted for body weight has led to correlated response in physical activity. In consequence, mice selected in the upward direction expend some of the excess energy intake rather than assimilating it as body mass and are, therefore, slightly leaner than their counterparts selected in the downward direction.
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    Theoretical and applied genetics 81 (1991), S. 720-728 
    ISSN: 1432-2242
    Keywords: Diallel cross ; Heterosis ; Maternal effects ; Mice
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    Topics: Biology
    Notes: Summary The influence of purebred selection on the combining abilities of five lines of mice was examined. Two replicated testcross diallels were made after 10 and 20 generations of purebred selection for litter size, weaning weight, weight gain, and feed efficiency. Average direct genetic effects were of major importance, followed by average maternal genetic effects. In all of the replications, between two and four out of ten crosses showed significant heterosis. Heterosis ranged from 0 to 38% in litter size, from 0 to 20% in weaning weight, from -11 to 11% in weight gain, and from -8 to 17% in feed efficiency. For litter size and weaning weight, heterosis estimates increased between 80 and 100% from generation 10 to 20. Weight gain and feed efficiency showed decreasing heterosis with partly negative estimates in the second diallel. Combinations exhibiting significant heterosis varied between replicates and between the two diallels.
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    Theoretical and applied genetics 82 (1991), S. 65-73 
    ISSN: 1432-2242
    Keywords: Mice ; Diallel cross ; Maternal heterosis ; Litter size ; Growth traits
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    Notes: Summary Results are presented from two replicated three-breed cross diallels that were conducted after 20 generations of selection for purebred performance in mice. The selection criteria for the different lines were: litter size at birth (LS), weaning weight at 4 weeks (WW), weight gain from week 4 to week 6 (WG), and body fat content at week 6 (FT). Additionally, a random-mating control line (C) was kept. Significant maternal heterosis was found in litter size and weaning weight. Estimates of maternal heterosis in litter size were very high, ranging from 17 to 50% of the mean of the corresponding single crosses. Maternal heterosis in weaning weight usually was negative and ranged from +9 to -11%. Significant maternal heterosis in feed efficiency and weaning weight could only be found in a few cases. Total performance of three-breed crosses was highly superior to that of single crosses and purebreds. Means of the corresponding purebreds or single crosses were of little use in predicting three-breed cross performance.
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    Theoretical and applied genetics 91 (1995), S. 340-345 
    ISSN: 1432-2242
    Keywords: Selection index ; Restricted index ; Fat ; Mice
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    Topics: Biology
    Notes: Abstract The objective of this study was to determine if low secondary selection differentials, caused by selecting within full-sib families, may have accounted for the failure of an intended restricted selection index to reduce epididymal fat pad weight (EF) without changing body weight (BW) in mice. Replicate lines that had been selected within full-sib families for high (HE) or low (LE) EF, while holding BW constant, were crossed. After two generations of random mating, two replicates were sampled and selection initiated for the same restricted index criteria except that mass selection was used to increase the selection differentials. In both phases of selection the HE restricted index selection, designed to increase EF without altering BW, was in agreement with expectation. In contrast, the LE index, designed to decrease EF without changing BW, did not agree with theory since BW increased while EF decreased only slightly. Therefore, reduced selection differentials could not explain the deviation from theory. A possible explanation may reside in the restricted selection index being more sensitive to changes in genetic parameters due to shifts in gene frequency as a consequence of the selection applied. However, linkage disequilibrium and genetic drift can not be ruled out as contributing factors to the asymmetry of response.
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    Theoretical and applied genetics 79 (1990), S. 268-272 
    ISSN: 1432-2242
    Keywords: Mice ; Lifetime ; Performance ; Longevity ; Selection
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    Notes: Summary An experiment was conducted in mice to examine whether selection can increase reproductive life and lifetime production of progeny. Mice in two lines with litter size standardized at birth and in two lines without standardization were pair-mated at 7 weeks of age and maintained as long as they produced litters up to 382 days. Progeny from the sixth litters were used to maintain the four selected lines, while progeny from the first litters were bred to maintain unselected control lines. Selected and control lines were compared at five and six generations of the selected lines. Contemporary comparisons revealed that the length of reproductive life and most lifetime production traits were significantly greater in the selected than in control lines. Realized heritability of the length of reproductive life ranged from 0.08 to 0.13. It was concluded that the length of reproductive life and lifetime production in mice can be increased by selection.
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    Theoretical and applied genetics 80 (1990), S. 625-630 
    ISSN: 1432-2242
    Keywords: Selection ; Mice ; Litter size ; Litter weight ; Reproductive performance
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    Topics: Biology
    Notes: Summary Five 60-pair lines of mice were selected for seven generations for the following criteria: number born alive (LSO), random selection of litters (LC), number born alive divided by the weight of the dam at 9 weeks (LSO/DWT), total litter weight weaned divided by the weight of the dam at 9 weeks (LWT/DWT), and weight of litter weaned (LWT). All traits were measured in the first parity only and litters were not standardized. Realized heritabilities for LSO, LWT, LSO/DWT, and LWT/ DWT were 0.10± 0.06, 0.11±0.07, 0.22 ± 0.04, and 0.22 ± 0.08, respectively. Selection response for the two ratio lines was due to correlated responses in the respective numerators, LSO and LWT, as DWT did not decrease. In terms of improving LWT, selection for LWT/ DWT was three times as effective as selection for LSO/ DWT.
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    Theoretical and applied genetics 84 (1992), S. 640-642 
    ISSN: 1432-2242
    Keywords: Mice ; Recombination ; Selection ; Chiasmata
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    Notes: Summary Chiasma frequency was measured in male mice of three outbred lines: FZt:DU (control); DU:6, selected for increased body weight; and DU:C, selected for high fertility. Chiasma frequency was seen to increase in the high body weight line, but decrease in the high fertility line. In both selected lines the intragroup variance in chiasma frequency increased while in DU:C the intracell variance was lower than in the control.
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    Theoretical and applied genetics 75 (1987), S. 177-188 
    ISSN: 1432-2242
    Keywords: Correlated responses ; Mice ; Body composition ; Growth ; Fat
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    Notes: Summary Correlated responses were estimated in each of two replicate lines of mice selected within full-sib families for high (HF) or low (LF) 12-week epididymal fat pad weight as a percentage of body weight (epididymal fat pad percentage), or high (HL) or low (LL) 12-week hind carcass weight as a percentage of body weight (hind carcass percentage). Two replicate control lines (RC) were maintained. Correlated traits were measured in each of the 10 generations of selection. Realized (rG R) and offspring-sire genetic correlations generally were in agreement. In HF and LF, 3–6 week postweaning gain (rG R = 0.36±0.04) and feed intake (rG R = 0.50±0.13) had positive correlated responses, but feed efficiency and feed intake/metabolic body size did not change. Positive correlated responses were found for subcutaneous fat pad percentage, body weight-adjusted subcutaneous fat pad weight and fat percentage in the hind carcass (rG R's were 1.04±0.13, 0.93±0.13 and 0.90±0.08). In the hind carcass, fat-free dry (protein + ash) percentage showed a small negative correlated response, and fat-free dry weight did not change. In HL and LL, the correlated responses for the above traits were generally opposite to those observed in HF and LF. Litter size, percentage of infertile matings, and preweaning mortality showed no consistent correlated responses in any of the lines, but an index of fitness combining the three traits showed a decrease in all four selection treatments.
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    Theoretical and applied genetics 75 (1988), S. 415-423 
    ISSN: 1432-2242
    Keywords: Mice ; Selection ; Gain ; Feed restriction
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    Notes: Summary Direct and correlated responses in weight gain and body weights were assessed for nine generations of within-family selection. Four selection criteria were used: gain between 28 and 38 or 48 and 58 days of age, and under two feeding regimes, i.e. ad libitum consumption or 80% of the control line. Direct responses to selection and realized heritabilities in the ad libitum lines were greater in the first period. Weight gain under ad libitum feeding at later ages appeared to have a lower genetic variability. In the restricted lines the responses and realized heritabilities were higher in the second period. Selection under restricted feeding in both periods led to animals that had lower weight gains than the control line when compared under ad libitum feeding.
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    Theoretical and applied genetics 75 (1988), S. 424-431 
    ISSN: 1432-2242
    Keywords: Mice ; Selection ; Body composition ; Gain
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    Notes: Summary Correlated responses in feed efficiency, feed consumption and body composition were investigated after nine generations of selection for weight gain in two age intervals, 28 to 38 or 48 to 58 days old, and under ad libitum feed consumption or intake restricted to 80% of the control lines. Correlated responses in feed efficiency and feed consumption in the ad libitum lines were positive in the early period and negative in the late period. Restricted lines had a positive response in feed efficiency and a negative response in consumption in both periods of selection. Changes in body composition in the early period were the same in all selected lines: a lower crude protein percentage at the start of the period and a lower ash percentage at the end of the period. Body composition at the start of the late period was not altered by selection, while at the end of the period ad libitum lines had higher dry matter percentages and restricted lines had lower fat and higher ash percentages. Body composition at 100 days old was not affected by selection except for dry matter percent, which was lower in the restricted lines.
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    Theoretical and applied genetics 78 (1989), S. 217-223 
    ISSN: 1432-2242
    Keywords: Correlated responses ; Fat depots ; Lean tissue ; Body composition ; Mice
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    Notes: Summary Development of adipose tissue in five depots was investigated in mice selected for high or low 12-week epididymal fat pad weight as a percentage of body weight (HF and LF lines), or high or low 12-week hind carcass weight as a percentage of body weight (HL and LL lines). An unselected control line (RC) was maintained. Hind carcass (HC) and fat pads from subcutaneous hindlimb, subcutaneous forelimb, gonads, kidneys and mesentery were dissected and weighed at 4, 6, 9, 12 or 15 weeks of age. Generally, body weight (BW), daily gain (DG), feed intake (FI), feed efficiency (FE) and feed intake/metabolic body weight (FC) were higher (P≤0.05) in HF than in LF, and in LL than in HL. HF had more fat (as a percentage of BW) than LF in all depots (P≲-0.01), and asymmetry (P≤0.01) was detected for gonadal fat. LL consistently had a higher (P≤0.01) fat percentage than HL, and asymmetry (P≤0.01) was observed for perirenal fat. At age of selection, ranking of fat depot weights as a percentage of total fat depot weight was not changed by selection; however, gonadal fat accounted for more of the total fat in HF and LL compared with RC, while the opposite was found in LF and HL. HC percentage was higher (P≤0.01) in HL than LL, and higher (P≤0.01) in LF than HF. Growth rate of each fat depot relative to BW was not affected by selection. These results demonstrated that selection for proportion of fat in one depot or for HC percentage changed fat percentage in other depots. However, the rate of fat deposition in each depot relative to body weight gain was not altered.
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    Theoretical and applied genetics 81 (1991), S. 685-692 
    ISSN: 1432-2242
    Keywords: IGF-1 ; Body weight ; Realized heritability ; Genetic correlation ; Mice
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    Notes: Summary Five generations of divergent selection for plasma concentration of insulin-like growth factor-1 (IGF-1) and for 12-week body weight were carried out in mice, including randomly selected control lines for each trait. All lines were replicated once (12 lines in total). Each replicate line consisted of eight male and eight female parents per generation. Litter size was standardized to eight pups at birth. Mass selection was applied in the selected lines and within-family random selection in the control lines. Blood was taken from the orbital sinus of individual mice at 12 weeks of age for IGF-1 assay. Realized heritabilities were 0.10±0.01 for IGF-1 and 0.41 ± 0.02 for 12-week weight. The realized genetic correlation between IGF-1 and 12-week weight was 0.58 ± 0.01, with a phenotypic correlation of 0.38. Although the genetic correlation between IGF-1 and body weight in mice is moderately positive, 12-week weight responded 3.5 times as fast to weight selection as to selection for IGF-1.
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    Theoretical and applied genetics 84 (1992), S. 307-312 
    ISSN: 1432-2242
    Keywords: Selection index ; Correlated responses ; Fat ; Fitness ; Mice
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    Topics: Biology
    Notes: Summary Correlated responses were studied in lines of mice selected for eight generations based on the criterion of a restricted selection index. Two replicate lines were selected in each treatment as follows: HE, high epididymal fat pad weight (EF) with zero change in body weight (BW) at 12 weeks of age; LE; low EF with zero change in BW; and RS, randomly. Correlated responses showed considerable variation between replicates, suggesting that genetic drift was important. Further, correlated responses for most traits were relatively small, probably because of low selection intensity. The HE line responded as expected in component traits of the restricted index. Associated compositional traits in HE responded as predicted since traits correlated with adiposity increased and hind carcass weight did not change significantly. Feed intake increased and feed efficiency (weight gain/feed intake) decreased in HE, as predicted. In contrast, the LE line did not respond in component traits as predicted since EF did not decrease and BW increased. Consequently, LE exhibited little change in traits associated with adiposity, but hind carcass weight, feed intake and feed efficiency increased. Of the correlated responses scored for fitness traits (littering rate, number of days from pairing of mate to littering, litter size and preweaning pup survival rate), significant effects were found for decreased littering rate in LE and increased prenatal survival rate in HE. In summary, correlated responses to restricted index selection generally agreed with expectation when responses in component traits of the index were considered.
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    Theoretical and applied genetics 88 (1994), S. 479-485 
    ISSN: 1432-2242
    Keywords: Correlated responses ; Embryos ; Cryoprotectant ; Mice
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    Topics: Biology
    Notes: Abstract Lines of mice selected for high (HF) or low (LF) 12-week epididymal fat pad weight as a percentage of body weight were used to investigate the effects of genotype, two cryoprotectants [glycerol (GLY) and propylene glycol (PG)] and genotype x cryoprotectant interaction on cryosurvival of four and eight-cell embryos. Embryos were collected from selection lines and reciprocal crosses of selection lines (HFLF and LFHF) and frozen by established slow-cool methods. Embryos were thawed for 40s at room temperature and then placed in a 37° C waterbath for 1 min. Cryoprotectant was diluted from embryos with either 0.5 M sucrose (GLY-treated) or 1.0 M sucrose (PG-treated). Post-thaw survival was measured as the percentage of embryos developing to 36 h (PTS36), 48 h (PTS48) and hatched blastocyst (PTSHB), respectively. Non-frozen controls were cultured concurrently with frozen embryos. No significant genotype or genotype x cryoprotectant interaction effects were found. Results of the embryo freezing study indicated that selection for high or low fat content did not affect the ability of embryos to survive cryopreservation. There was no indication of embryo heterosis for post-thaw survial. Embryos frozen with GLY survived the freeze-thaw stress significantly better than those frozen in PG (P 〈 0.05). In vitro development of non-frozen controls at 36 and 48 h did not vary significantly among lines, but in vitro development was significantly different among lines at the hatched blastocyst stage (P 〈 0.05). Linear contrasts showed that the embryonic genome was responsible for differential in vitro development at the hatched blastocyst stage between these selected lines (HF 〉 LF; P 〈 0.05); asymmetric response also occurred in that both HF and LF exceeded the unselected control line (P 〈 0.05).
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    Theoretical and applied genetics 64 (1983), S. 275-281 
    ISSN: 1432-2242
    Keywords: Fused gene ; Mice ; Hydrocortisone ; Gene inactivation
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    Topics: Biology
    Notes: Summary This study was undertaken to examine the effects of hydrocortisone injected into male mice on the phenotypic expression and inheritance of the Fused (Fu) gene in their offspring. Data were obtained indicating that there is a hydrocortisone-susceptible period during spermatogenesis. Hydrocortisone injections of males during this period resulted in a statistically significant decrease in the proportion of phenotypically Fu offspring. Genetic analysis with the use of the closely linked recessive marker tufted (tf) demonstrated that the deficit of phenotypically Fu individuals among offspring is not caused by the differential death of gametes, zygotes or embryos. According to genetic data, this deficit is due to a decrease in the penetrance of the Fu gene and partly to its inherited inactivation. The possible mechanisms of the observed phenomenon are discussed.
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    Theoretical and applied genetics 67 (1984), S. 113-122 
    ISSN: 1432-2242
    Keywords: Mice ; Selection ; Growth ; Genetic correlation
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    Notes: Summary Four lines of mice were formed from a common base population and selected for 37 generations for either increased 3-week weight (weaning weight), 6-week weight, 3–6 week gain, or maintained as a randomly bred control line. Realised heritability estimates for short-term (long-term) responses were 0.33±0.20 (0.07±0.10), 0.46±0.14 (0.26±0.09), 0.36±0.14 (0.24±0.11) for 3-week weight, 6-week weight and 3–6 week gain, respectively. Realised genetic correlations estimated from short-term (long-term) responses were 0.23±0.08 (0.35±0.10) between 3-week weight and 3–6 week gain; 0.82±0.04 (0.58±0.08) between 3-week weight and 6-week weight; and 0.81±0.04 (0.97±0.04) between 3–6 week gain and 6-week weight. The genetic correlation between 3-week weight and 6-week weight was asymmetric with a greater correlated response for 3-week weight when selecting for 6-week weight (1.06) than vice versa (0.63).
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    Theoretical and applied genetics 69 (1985), S. 447-455 
    ISSN: 1432-2242
    Keywords: Crossbreeding ; Lifetime performance ; Mating system ; Mice
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    Topics: Biology
    Notes: Summary Mating systems that capitalize on heterosis in dairy cattle are the criss-cross (CC), the repeat hybrid male cross (RHMC) and random mating within a synthetic population (SYN). When performance is determined solely by direct additive genetic and dominance genetic effects, expected performance under CC (averaged over four generations after F1 generation), relative to that under RHMC (or SYN) is (59 G1+69 G2 +82 H)/64(G1+G2+H), where Gi is direct additive genetic effect of breed i and H is direct heterosis. Five CC, five RHMC and one SYN population of mice were prepared to test 533, 534 and 410 females, respectively for performance during lifetime (155 days after mating). Each female was pair-mated at day 42 with a male from the SYN population and the number of lactations during the lifetime (NL), total number (TN) and weight (TW in g) of young born alive during lifetime, total number (AN) and weight (AW in g) of young raised to weaning (18 days), and actual length of reproductive life (RL in days) were recorded. Observed performance averaged over four generations was, under CC, RHMC and SYN, 4.74, 4.62 and 4.56 for NL, 49.9, 48.2 and 48.8 for TN, 86.0, 83.6 and 85.1 g for TW, 47.5, 45.5 and 46.3 for AN, 512.1, 517.9 and 521.1 g for AW, and 120.0, 117.6 and 116.7 for RL, respectively. Heterosis due to the female (H) was 10, 30, 33, 34, 43 and 9% for NL, TN, TW, AN, AW and RL, respectively. Direct additive genetic values were estimated for each pair of lines involved with CC or RHMC. These values were used in the formula to calculate expected performance in each mating system. The ratio of CC to RHMC for the expected and observed performance was 1.01 and 1.01 for NL, 1.04 and 1.04 for TN, 1.04 and 1.03 for TW, 1.04 and 1.04 for AN, 1.05 and 0.99 for AW, and 1.01 and 1.02 for RL, respectively. The ratio of CC to SYN for the observed performance was 1.04 for NL, 1.02 for TN, 1.01 for TW, 1.03 for AN, 0.98 for AW, and 1.03 for RL. As expected, the observed mean performance under CC was slightly larger than that under RHMC or SYN.
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    Theoretical and applied genetics 74 (1987), S. 793-801 
    ISSN: 1432-2242
    Keywords: Mice ; Fat ; Lean tissue ; Selection ; Heritability ; Genetic correlation
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    Topics: Biology
    Notes: Summary Replicated within full-sib family single-trait selection was conducted for 10 generations in mice for (1) high or low 12-week epididymal fat pad percentage (100 x epididymal fat pad weight/body weight) or (2) high or low 12-week hind carcass percentage (100 x hind carcass weight/body weight). Pooled realized heritabilities based on high, low and divergent selection were 0.66±0.09, 0.65±0.13 and 0.66±0.05 for epididymal fat pad percentage and 0.48±0.08, 0.33±0.08 and 0.40±0.04 for hind carcass percentage. The pooled realized genetic correlation (rG R) between epididymal fat pad percentage and hind carcass percentage based on divergence was −0.67±0.04. Other estimates of (rG R) were: epididymal fat pad percentage with body weight (0.57±0.05); epididymal fat pad percentage with epididymal fat pad weight (1.17±0.05); hind carcass percentage with body weight (−0.61±0.09); hind carcass percentage with hind carcass weight (−0.05±0.11). Indirect measures of fat and lean tissue percentages were highly heritable, and (rG R) between them would be desirable from the standpoint of analogous types of traits in livestock. In the same context, undesirable (rG R)'s were found between epididymal fat pad percentage and body weight and between hind carcass percentage and body weight.
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    Theoretical and applied genetics 71 (1985), S. 52-56 
    ISSN: 1432-2242
    Keywords: Heterosis ; Reproduction ; Mice ; Body weight
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    Topics: Biology
    Notes: Summary To examine the effect of selection for body weight on levels of heterosis for reproductive traits, crosses were made between three groups of six lines of mice, one group unselected (controls) and the other two selected for high (large lines) and low (small lines) 6-week body weight, respectively. The coefficient of inbreeding of each line was about 0.60. In a comparison of purebred and crossbred progeny, both out of purebred mothers, there was on average 4% heterosis for number born, 3% for percentage weaned and 8% for numbers weaned. In a comparison of purebred and crossbred mothers, each mated to males of an unrelated strain and dissected on the 17th day of gestation, crossbreds had on average 1.6 more live embryos, which was 22% of the purebred mean. This comprised an increase of 0.6 corpora lutea, of 0.4 in survival to implantation and of 0.6 in subsequent survival to 17 days. The heterosis was similar whether the mothers had parents of the same or different size.
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    Theoretical and applied genetics 76 (1988), S. 467-472 
    ISSN: 1432-2242
    Keywords: Selection ; Embryo development ; Embryo culture ; Mice
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    Topics: Biology
    Notes: Summary Replicated divergent selection was conducted for two generations in ICR mice for in vitro developmental capacity (IVDC; percentage of fertilized one-cell zygotes developing to blastocysts in vitro per female donor). Realized heritabilities based on high and low selection were 0.03±0.08 and −0.11±0.09 in replicate 1, and 0.10±0.11 and 0.08±0.10 in replicate 2. No differences were detected between selection lines (P〉0.2) or replicates (P〉0.1). Estimate of heritability in the base population based on 332 daughter-dam pairs was 0.14±0.18. These results indicate that additive genetic variance contributes little to the phenotypic variance in this trait. Considerable phenotypic variation in IVDC was observed (mean=49.3; SD=31.0), with a range of IVDC from 0%–100%. Utilization of donor female as a blocking factor is suggested for designs of experiments with preimplantation embryos to increase precision and power of statistical analyses.
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    Theoretical and applied genetics 59 (1981), S. 129-137 
    ISSN: 1432-2242
    Keywords: Selection ; Mice ; Feeding Efficiency ; Correlation
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    Topics: Biology
    Notes: Summary Selection was practised for improved feed efficiency (gain/feed intake) of mice on two alternative feeding regimes. In one set of lines animals were fed ad libitum, in the other set they were individually fed a fixed amount of feed (about 10% below the control ad libitum intake) which was not changed over generations. For each treatment, a pair of replicate lines (E) were selected on efficiency from 3–5 weeks of age for 8 generations and another pair (L) from 5–7 weeks for 7 generations. A control line was maintained for both E and L lines. In terminal generations mice from each line were tested on each feeding regime, and carcasses of ad libitum fed mice were analysed. The realized heritability (within families) for efficiency averaged 13%, without much variation over treatments. In the E lines efficiency increased by about 18% of the control mean and in the L lines by about 60%, although absolute changes were small, and responses were similar on the two feeding regimes. Weights at the start of test decreased in the E lines and increased in the L lines; weights at the end of test increased in both. When tested on the alternative regimes, no interactions were detected for live weights, weight gains or efficiency; selection under fixed intake led to the same increase in appetite as did that under ad libitum. There were no interactions for carcass composition. Selection for efficiency led to an increase in fatness on both selection regimes and both weight ranges.
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    Theoretical and applied genetics 73 (1986), S. 148-157 
    ISSN: 1432-2242
    Keywords: Mice ; Correlated responses ; Organ growth ; Degree of maturity ; Allometry
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    Topics: Biology
    Notes: Summary Correlated responses to selection for increased 3–6 week postweaning gain in male mice were estimated for seven internal organs (testes, spleen, liver, kidneys, heart, small intestine (S intest) and stomach) weighed at specific degrees of maturity in body weight (37.5, 50.0, 62.5, 75.0, 87.5 and 100%). Correlated responses in organ weights were generally large, but the magnitude and direction of response depended upon whether 1) comparisons were made at the same age, degree of maturity or body weight and 2) absolute or proportional organ weights were used. The selected line (M16) weighed more and had larger organ weights than controls (ICR) when compared at either the same degree of maturity or the same age, indicating positive genetic correlations between body weight and the respective organ weights. Positive correlated responses were found in spleen weight/body weight at all degrees of maturity and in liver and S intest weights as a proportion of body weight at some degrees of maturity. Testes, kidneys, heart and stomach weights as a proportion of body weight had negative correlated responses, though this was consistent only for kidneys across all degrees of maturity. Correlated responses in organ weights adjusted for body weight by covariance analysis were positive for spleen, S intest and stomach and negative for testes and kidneys. Based on the constrained quadratic model, degree of maturity in organ weight relative to degree of maturity in body weight responded positively for testes, kidneys and S intest and negatively for spleen and liver. Selection for increased growth caused negative correlated responses in allometric growth of testes, kidneys, S intest and stomach.
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    Theoretical and applied genetics 75 (1987), S. 147-150 
    ISSN: 1432-2242
    Keywords: Mice ; Selection experiments ; Maternal effects litter size manipulation ; Fertility
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    Topics: Biology
    Notes: Summary A short-term selection experiment for increasing the first-day litter size (LS1) and 28-day litter weight (LW28) was conducted with three populations of mice over 8 generations. Different methods of litter size manipulation were used for the populations — in S the litter size was standardized to 8 (4 ♂ ♂, 4 ♀♀) on the first day, in LA it was adjusted to the average size of all litters born on the same day and NL had the natural litter size. To eliminate temporary environmental effects, a control population was kept in each case. The selection results per generation were, for LS 1 b=0.30 (S, NL) and 0.20 (LA), and for LW28 b=5.62 g (S), 5.26 g (NL), and 4.32 g (LA). The heritability obtained was between 0.18 and 0.13 for LS 1 and from 0.42 to 0.12 for LW28. The populations differed in the correlated responses for body weight parameters (litter weight gain). The implantation rate increased in populations S and NL (b=0.19, 0.37), but not in population LA. Postnatal mortality went down (b=-0.07) and the dam's milk production rose (b=1.11 g) only in population LA. The estimated partial regression coefficient linking body weight at mating (BWM) for the dam and the daughter's litter size showed an effect on the litter size.
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    Theoretical and applied genetics 71 (1985), S. 250-257 
    ISSN: 1432-2242
    Keywords: Mice ; Lifetime ; Performance ; Additive ; Maternal ; Heterosis
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    Topics: Biology
    Notes: Summary A total of 2,457 lifetime performance records of 29 genetic groups of mice was analyzed using multiple regression of records on the proportion of gene contribution from 6 lines (designated as Lines MP, mQ, WP, wQ, CP and cQ). Genetic effects were partitioned into line additive, line maternal, direct heterosis, maternal heterosis and paternal heterosis effects. The line additive and line maternal effects were expressed as deviations from Line cQ. Seventeen of 25 line additive effects differed significantly (P〈0.05) from Line cQ whereas only 4 of 25 line maternal effects deviated significantly from Line cQ. Deviations in line additive effects from cQ were negative in all lines examined whereas deviations in line maternal effects from cQ were all positive, indicating a negative relationship between line additive and line maternal effects. Direct heterosis effects were all positive and significant (P 〈 0.01) except in the MPxWP cross which was produced by mating Lines MP and WP of the same base population (P). Maternal heterosis effects were significant in 10 of 20 cases whereas paternal heterosis effects were significant in 13 of 20 cases. Although direct heterosis is a major component of total heterosis effects (sum of direct, maternal and paternal heterosis), the results suggest that parental heterosis may need to be considered in producing multiple way crosses. The fitting of line additive, line maternal, direct heterosis, maternal heterosis and paternal heterosis effects in the multiple regression model effectively accounted for all genetic effects in lifetime performance.
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  • 45
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    Theoretical and applied genetics 51 (1978), S. 249-260 
    ISSN: 1432-2242
    Keywords: Mice ; Maternal Effects ; Body Weight ; Maturity ; Sex-linkage
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    Topics: Biology
    Notes: Summary Direct and maternal genetic effects were evaluated for maturing patterns of body weight in mice using a crossfostering design. Crossfostering was performed in one group using dams from populations selected for rapid growth rate (M16 and H6) and their reciprocal F1. crosses. A second crossfostering group consisted of dams from the respective control populations (ICR and C2) and their reciprocal F1. 's. Population differences were partitioned into direct and maternal effects due to genetic origin, correlated selection responses, heterosis and cytoplasmic or sex-linked effects. Degree of maturity was calculated at birth, 12, 21, 31 and 42 days of age by dividing body weight at each age by 63-day weight. Absolute and relative maturing rates were calculated in adjacent age intervals between birth and 63 days. Genetic origin effects (ICR vs. C2; M16 vs. H6) were significant for many maturity traits, with average direct being more important than average maternal genetic effects. In general, correlated responses to selection for maturity traits were larger in the M16 population (M16 vs. ICR) than in the H6 population (H6 vs. C2) and correlated responses in average direct effects were larger than average maternal effects. Positive correlated responses in average direct effects were found for relative maturing rates at all ages and for absolute maturing rates from 31 to 63 days. Apparent correlated responses in degree of maturity were negative for M16 and H6. However, further analysis suggested that the correlated response for degree of maturity in H6 may be positive at later ages and negative at earlier ages. Direct and maternal heterosis for degree of maturity was positive in the selected and control crosses. Absolute and relative maturing rates showed positive heterosis initially, followed by negative heterosis. Reciprocal differences due to the cytoplasm or sex-linkage were not important for patterns of maturity.
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    Theoretical and applied genetics 65 (1983), S. 17-23 
    ISSN: 1432-2242
    Keywords: Diallel cross ; Maternal effects ; Heterosis ; Mice
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    Topics: Biology
    Notes: Summary A genetic framework was developed for the interpretation of statistical parameters estimated from a diallel experiment among a fixed set of lines. These included average direct genetic, average maternal genetic, general combining ability, reciprocal, and line and specific direct and maternal heterotic effects. The genetic model is based on direct and maternal additive and dominance genetic effects as would be expected in animal species. The model assumes that dominance is the underlying basis of heterosis. As an example, litter size at birth was analyzed from a 5 × 5 diallel cross with mice.
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    Theoretical and applied genetics 55 (1979), S. 209-223 
    ISSN: 1432-2242
    Keywords: Maternal effects ; Body composition ; Selection ; Growth ; Mice
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    Topics: Biology
    Notes: Summary The effect of the postnatal maternal environment, simulated by rearing mice in litters of three, six or nine, on body weight and body composition was investigated in three lines of mice differing widely in growth rate. The lines were selected for high (H6) and low (L6) 6-week body weight while the control line was maintained by random selection. Body weight and weights and percentages of ether extract, water, ash and protein at 21, 42, 63 and 84 days were recorded. With few exceptions, there were positive correlated responses to selection in body weight and in weights of body components. At 21 and 42 days the correlated responses were larger in L6 mice than in H6 mice. Body weight and weights of body components were larger for mice reared in litters of three than for those reared in litters of nine. Also, mice reared in litters of six were intermediate in body weight and weights of some of the body components between those reared in litters of three and nine. Differences in body weight and weights of body components due to postnatal maternal environment were small by comparison with differences due to genetic line. There were significant line by maternal environment interactions in body weight at 21 days and in ether extract weight at 21 and 63 days. Line and maternal environment differences in percentages of body components did not follow any consistent trend. The results for percentages of body components were further complicated by line x maternal environment interactions. In general, both line and postnatal maternal environmental differences in percentages of body components diminished with age.
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    Theoretical and applied genetics 50 (1977), S. 179-184 
    ISSN: 1432-2242
    Keywords: Mice ; Feed Efficiency ; Body Composition ; Protein Content ; Selection
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    Topics: Biology
    Notes: Summary An examination was carried out of the feed intake, feed efficiency and body composition of selected and unselected mice. It was demonstrated that selected mice utilised food more economically, and, in total, produced more protein than the control animals. However, selection had a negative influence on the percentage content of protein and ash. Also, selection caused greater adiposity of selected females and a greater water content in the bodies of selected males (in %).
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    Theoretical and applied genetics 51 (1977), S. 119-125 
    ISSN: 1432-2242
    Keywords: Mice ; Cross-nursing Technique ; Body Weight ; Prenatal and Postnatal Maternal Influences
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    Topics: Biology
    Notes: Summary The cross-nursing technique was used to assess the relative importance of prenatal and postnatal maternal influences on growth in mice from an unselected population originated from a cross of four highly inbred strains. Body weights were studied at birth, 7-, 14-, 21- and 42-days, in addition to the weight gains between these ages and tail length at 21 and 42 days of age. At littering, each dam in each nursing set retained two of her own offspring and two were transfereed to each of the other dams in the set, so that each nursed litter contained six young representing three mothers. Prenatal influences accounted for 37, 15, 10, 11 and 13 % of the total variation in the respective body weights, while postnatal influences accounted for 0, 64, 65, 49 and 14% at the respective ages. In the case of weight gains, prenatal influences were responsible for 16, 4, 6 and 30%, while postnatal influences were responsible for 66, 66, 31 and 7% of the total variation in gain during the respective four periods examined. Apparently the individual weight gain from 7 to 14 days was a better measure of the lactational performance of the dam than individual 14-day weight. For tail length, prenatal influences accounted for 6 % and 4 % of the total variation in tail length at 21 and 42 days, respectively, while postnatal influences accounted for 60 % and 24 % at the respective ages. Generally, there was no indication of an important interaction between the nurse and the nursed young at any stage studied.
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    Theoretical and applied genetics 55 (1979), S. 279-284 
    ISSN: 1432-2242
    Keywords: Mating system ; Selection ; Mice
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    Notes: Summary A reticulate mating system is described which was designed by the late R.A. Fisher to permit the introduction of new genetic variability into an improved stock by immigration. Analysis of part of a long-term experiment to alter the degree of dominance of the mutant Sd in mice using the system demonstrates a rapid response. Its applicability to stocks of animals of economic value is considered.
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    Theoretical and applied genetics 55 (1979), S. 57-64 
    ISSN: 1432-2242
    Keywords: Mice ; Selection ; Growth curve
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    Topics: Biology
    Notes: Summary The weights of mice in lines selected for different combinations of high and low body weights at 5 and at 10 weeks of age were recorded from 3 to 21 weeks of age. The average growth curve for each line was computed using the Gompertz function. The growth curves of lines selected for high or low weight at a single age (ST lines) showed large differences in estimates of mature size and small differences in estimates of maturing rate, i.e. of the relative rate of growth to maturity. The growth curves of lines selected by independent culling for divergent combinations of deviations of opposite sign in 5- and 10-week weights (ICL lines) showed little difference in estimates of mature size and a large difference in estimates of maturing rate. The growth curves of lines selected by index for divergence in 5-week weight with no change in 10-week-weight or for divergence in 10-week-weight with no change in 5-week weight showed large differences in estimates of mature size and large differences in estimates of the maturing rate. The relationship between mature size and maturing rate was affected in different ways by the three types of selection.
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    Theoretical and applied genetics 57 (1980), S. 209-220 
    ISSN: 1432-2242
    Keywords: Mice ; Early puberty ; Litter size ; Selection ; Reproductive rate ; Pheromone
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    Topics: Biology
    Notes: Summary The influence of male-induced early puberty on female reproductive rate was determined in three lines of mice differing in litter size and body weight. The lines originated from a single base population and had undergone 20 generations of selection for the following criteria: large litter size at birth (L+), large litter size and small 6-week body weight (L+W−), or small litter size and large 6-week body weight (L−W+). Females were paired with a mature intact male of the same line at 3, 5 or 7 weeks of age. Mean mating age, averaged over lines, was 26.5 ± .3, 38.3 ± .3 and 52.7 ± .3 days. Exposure to a mature male accelerated female sexual maturation in each line. When contrasted with their sibs mated at a later age, early-pregnant females from each line exhibited a decline in one or more component of reproductive performance, suggesting that the physiological state of the very young female was not optimum for normal pregnancy. In comparisons of early and later mating ages, all three lines showed a decreased littering rate at first mating, number born alive, and individual birth weight of progeny adjusted for litter size; L+ and L+W− mice showed an increased perinatal mortality rate; L+ and L−W+ had a reduction in litter size at birth. When the L+, L+W− and L−W+ lines were compared with an unselected strain and a line selected for high postweaning gain in similar experiments, a genotype by environment interaction was apparent since all lines did not respond in a similar manner to early mating. The line ranking for litter size at birth for each age at male-exposure was L+〉L+W−〉L−W+, despite the significant line by age interaction. When litter size was adjusted by covariance for body weight at mating, the significant effects of age at male-exposure and line by age interaction were eliminated. All fertile females were remated after they had weaned their first litter to obtain information on litter size in parity two. Line differences in litter size at birth and number born alive were uniform across parities. An age by parity interaction was evident since the decreased fecundity at younger ages of male exposure in the L+ and L−W+ litters of parity one was not evident in parity two. Litter feed efficiency during first parity gestation was defined as litter birth weight divided by either cumulative feed intake of the dam from mating to parturition (GEI) or cumulative feed intake from weaning to parturition (GEII). The ranking of lines for GEI and GEH was L+〉 L+W−〉L−W+, but when feed efficiency was adjusted for littering rate, L+W− and L−W+ were not significantly different. With regard to age at mating, the ranking for GEI (7 wk 〉 5 wk 〉 3 wk) was reversed from GEII (3 wk 〉5 wk 〉 7 wk) and these significant differences were maintained after adjustment for littering rate.
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    Theoretical and applied genetics 54 (1979), S. 169-175 
    ISSN: 1432-2242
    Keywords: Mice ; Reciprocal crossing of lines ; Accumulated response to selection free of inbreeding
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    Topics: Biology
    Notes: Summary Mass selection of mice was conducted in populations of various size for 16 generations. Each selected population (E) corresponded to an analogous unselected population (C). The experiment was conducted in three replicates. After the 16th generation the replicates of the selected and control lines were crossed. Reciprocal crossing within the control lines gave better results than reciprocal crossing of the selected lines, despite the fact that the selected mice were characterised by a higher inbreeding coefficient. Larger effects were also obtained when crossing smaller rather than larger populations. This result is understandable since the animals from the smaller populations were characterised by higher inbreeding coefficients. The effect of heterosis was higher upon crossing the control lines rather than the selected ones and this caused a decreased the response to selection in almost all the traits investigated.
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    Lasers in medical science 1 (1986), S. 125-130 
    ISSN: 1435-604X
    Keywords: Wound contraction ; Fibroblasts ; Infrared laser ; Helium-neon laser ; Mice
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    Topics: Medicine , Physics , Technology
    Notes: Abstract The effect was investigated of combined pulsed infrared and continuous wave heliumneon mid-laser therapy on wound contraction and wound bed cellularity, and the effects were compared of variation in the infrared pulsing frequency. The laser used was the Space Mix-5 Mid-Laser and the wounds studied were full-thickness excised skin lesions made in the flank skin of CD1 adult female mice, which were maintained under general anaesthesia during both excision and irradiation. Treatment at 700 Hz increased wound contraction in comparison with treatment at 1200 Hz, when all other controllable parameters were kept constant. By 11 days after injury the cellularity of the wound bed was greater in the wounds treated with 700 Hz than in those treated with 1200 Hz, with the greatest difference being found in the number of fibroblasts, the cells primarily responsible for wound contraction.
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    Cellular and molecular life sciences 41 (1985), S. 73-74 
    ISSN: 1420-9071
    Keywords: Mice ; circling behavior ; phencyclidine ; naloxone ; hyperactivity
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    Topics: Biology , Medicine
    Notes: Summary Phencyclidine (PCP), when given to mice, induces general hyperactivity and rapid circling, similar to that caused by morphine. These effects are partially antagonized by naloxone.
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    Cellular and molecular life sciences 41 (1985), S. 1184-1186 
    ISSN: 1420-9071
    Keywords: Mice ; phospholipids ; kidney growth
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    Topics: Biology , Medicine
    Notes: Summary During the first 40 days of life the rate of incorporation of32P into total phospholipids and into phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, sphingomyelin, diphosphatidylglycerol, phosphatidic acid and phosphatidylinositol of mouse kidney was by some 25–35% higher than in older animals. Results suggest a different involvement of cellular membranes during of normal and compensatory renal growth.
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  • 57
    ISSN: 1420-9071
    Keywords: Mice ; glucan treatment ; Co60-irradiation ; stem cells, pluripotent ; granulocytes ; macrophages ; erythroid progenitor cells ; hemopoietic stomal cells ; hemopoiesis
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    Topics: Biology , Medicine
    Notes: Summary Glucan, a beta-1, 3 polyglucose, was administered to mice either 1 h before or 1 h after a 650 rad exposure to cobalt-60 radiation. Compared to radiation controls, glucan-treated mice consistantly exhibited a more rapid recovery of pluripotent stem cells and committed granulocyte, macrophage, and erythroid progenitor cells. This may partially explain the mechanism by which glucan also enhances survival in otherwise lethally irradiated mice.
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    Cellular and molecular life sciences 41 (1985), S. 498-500 
    ISSN: 1420-9071
    Keywords: Mice ; pregnant ; aminoglutethimide phosphate ; mice ; liver ; fetal ; erythroid colony-forming cells
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    Topics: Biology , Medicine
    Notes: Summary Pretreatment of pregnant mice with aminoglutethimide phosphate, an inhibitor of glucocorticoid synthesis, increases the content of fetal liver erythroid colony-forming cells (CFU-E), as assessed by the formation of erythroid colonies in vitro by fetal liver cells in plasma clots containing exogenous erythropoietin. In addition, the inability of aminoglutethimide to influence erythroid colony formation in vitro suggests that endogenous glucocorticoids exert a suppressive effect on the number of functional CFU-E in the fetal liver.
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  • 59
    ISSN: 1573-0832
    Keywords: Cryptococcus ; Immunity ; Immunohistology ; Meningoencephalitis ; Mice
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    Topics: Biology , Medicine
    Notes: Abstract An immunohistological study of L3T4(CD4)+ and LYT-2(CD8)+ lymphocytes, Mac-1(CD11b)+ monocytes and granulocytes in experimental murine cryptococcal meningoencephalitis was conducted. To assess the concomitant inflammatory reaction in an extracerebral site, livers were examined in parallel. Mice were infected i.v. withCryptococcus neoformans, group A/D, and organs were examined immunohistologically for CD4-, CD8- and monocyteand granulocyte-specific CD11b-phenotypic leukocytes over a period of 60 days. Intracerebrally, agglomerations of cryptococci formed pseudocysts that were surrounded by CD4+ and CD8+ lymphocytes at the end of the second week post-infection, followed by the invasion of monocytes and granulocytes into the lesions. After the fourth week post-infection, most of the invaded lesions were transformed into glious scars. Meningitis was usually marked and showed a homogenous distribution of CD4-, CD8- and CD11b-phenotypic cells, with a predominance of monocytes and CD4+ lymphocytes. Inflammatory infiltrates in the liver were found already 4 days post-infection. CD4+ lymphocytes and monocytes were distributed homogenously in the infiltrates, with a lower number of CD8+ lymphocytes being located rather in the periphery of the infiltrates. Comparing leukocyte kinetics in brain and liver, an important observation was the delayed immigration of immune cells at the intracerebral cryptococcal lesions as compared with the liver, and the different migration patterns of T-lymphocyte subgroups and macrophages. These results suggest that there are differential leukocyte migration patterns in the liver and brain following disseminated cryptococcosis. The immunological aspects of the observed leukocyte kinetics are discussed.
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    Mycopathologia 125 (1994), S. 33-39 
    ISSN: 1573-0832
    Keywords: Aflatoxin ; Lymphocytes ; Mice ; Ultrastructure
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    Topics: Biology , Medicine
    Notes: Abstract This investigation sought to determine whether splenic lymphocytes obtained from Balb/C mice exposed to aflatoxin B1 (AFB1) showed any ultrastructural changes which could account for the immunodysfunction attributable to aflatoxins. Lymphocytes obtained from Balb/C mice administered aflatoxin B1 in olive oil daily for three weeks were studied using both transmission and scanning electron microscopy. The lymphocytes demonstrated ultrastructural changes primarily in the mitochondria where marked internal dissociation of the cristae was revealed by transmission electron microscopy. All other cellular organelles were unaffected. No significant alterations in external structure were observed under scanning electron microscopy. The findings of this study indicate that AFB1 administration does not affect the surface topography of lymphocytes, but AFB1, by causing extensive mitochondrial damage, may affect the way in which these cells function. This could be a possible explanation for the immunodysfunction associated with AFB1.
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  • 61
    ISSN: 1573-0832
    Keywords: Cryptococcus ; Host defense ; Lymphocyte subsets ; Mice ; Mixed Lymphocyte Reaction
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    Topics: Biology , Medicine
    Notes: Abstract Cell-mediated immunity plays an important but incompletely understood role in host defense againstCryptococcus neoformans. Because of their multiple capacities as cytokine-secreting cells, cytotoxic cells, and antigen-specific suppressor cells, CD8 positive T lymphocytes could potentially either enhance or impair host defense againstC. neoformans. To determine whether CD8 T cells enhance or inhibit host defence during an infection with a highly virulent strain ofC. neoformans, we examined the effect of in vivo CD8 cell depletion on suNival and on the number of organisms in mice infected by either the intratracheal or intravenous routes. Adequacy of depletion was confirmed both phenotypically and functionally. Regardless of the route of infection, we found that survival of mice depleted of CD8 T cells was significantly reduced compared to undepleted mice. Surprisingly, however, CD8 depletion did not alter organism burden measured by quantitative CFU assay in mice infected by either route. These data demonstrate that CD8 positive T cells participate in the immune response to a highly virulent strain ofC. neoformans. By contrast to minimally virulent isolates that do not cause a life threatening infection, the immune response to a highly virulent isolate does not alter the burden of organisms, but does enhance host defense as it is necessary for the optimal survival of infected mice.
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    Behavior genetics 14 (1984), S. 1-19 
    ISSN: 1573-3297
    Keywords: Mice ; alcohol ; selective breeding ; pharmacogenetics ; biometrical genetics
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    Topics: Biology , Psychology
    Notes: Abstract A classical Mendelian cross was derived from Long-Sleep (LS) and Short-Sleep (SS) mice, lines selectively bred for differences in response to hypnotic doses of ethanol (ETOH). Biometrical genetic procedures applied to the selection phenotype, namely, duration of the ETOH-induced loss of the righting reflex, suggest that a simple additive genetic system controls this depressant response. Sex differences were present in the Mendelian cross generations that had the longest duration responses. An estimate of the number of loci differentiated by the selection was nine. Blood ethanol levels at the time of regaining the righting reflex in the seven genotypes of the Mendelian cross showed that the selection operated solely by changing tissue sensitivity to ethanol.
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  • 63
    ISSN: 1573-3297
    Keywords: Mice ; ultrasonic calls ; infants ; individual differences ; signatures
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    Topics: Biology , Psychology
    Notes: Abstract Infant house mice, Mus musculus, produce ultrasonic calls that reliably lead to retrieval by adult mice. While individual differences in calls have been demonstrated both among and within species, the influences of age and sex on call characteristics have not been systematically investigated in mice. This study examined the influences of age, sex, and genotype (inbred versus hybrid) on the rate, length, and frequency characteristics of the calls of 486 male and female mice from 2 to 12 days of age. Rate of calling followed a shallow inverted U-shaped function across days. Call lengths decreased and call frequency characteristics increased, in a linear manner, with age. Females emitted fewer calls, with a smaller bandwidth, at some ages than males. Hybrid pups produced more calls of greater length and a lower frequency than inbred pups. These results indicate the presence of cues that could allow adult mice to behave differentially toward pups as a function of their age and sex.
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    Behavior genetics 26 (1996), S. 463-470 
    ISSN: 1573-3297
    Keywords: Mice ; agonistic behavior ; aggression ; homogeneous set ; standard tester ; social behavior
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    Topics: Biology , Psychology
    Notes: Abstract Though social behavior has not been overlooked by behavior geneticists, the number of studies is small when compared to those on individual traits. One reason for the neglect may be the difficulty of making connections between genes and social behaviors, which by definition involve the interaction of two or more organisms. Fuller and Hahn (1976) addressed this issue and described three means of establishing social groups that would facilitate genetic analysis. We survey the literature on agonistic behavior in mice from 1976 through 1994 and describe interesting uses of those three methods. One of those methods (the standard tester design) often employs a “noninteractive” social partner. We present data showing that the standard tester design may be more valuable when using an evocative and interactive standard tester.
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    Behavior genetics 24 (1994), S. 493-496 
    ISSN: 1573-3297
    Keywords: Mice ; cross-transferring ; sibling reunion ; analgesia ; kin recognition mechanisms
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    Topics: Biology , Psychology
    Notes: Abstract The kin selection theory predicts that individuals would behave differently toward one another, depending on their genetic relatedness. Kin discrimination has been demonstrated in mice from social behavior, and previous familiarity, as well as familiarity with the partner's phenotype, has been postulated to represent proximate mechanisms. It has already been demonstrated that siblings' reunion resulted in a decrease in pain sensitivity that is mediated by endogenous opioids. In this study, using a cross-transferring design, it is shown that genetic relatedness with the male partner, independently of postnatal association, is responsible for changes in nociceptive threshold. Conversely, previous association till weaning has no effect on pain sensitivity. These data suggest that endogenous opioids activity and social behavior represent indices of different processes: the recognition of related animals and the discrimination of familiar (and also usually related) subjects, respectively.
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    ISSN: 1573-3297
    Keywords: Mice ; ultrasounds ; ultrasonic calls ; infants ; diallel cross ; individual differences
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    Topics: Biology , Psychology
    Notes: Abstract Ultrasonic calls produced by young mice reliably elicit investigation and retrieval by adults. While there are large individual differences in the characteristics of these calls, little work has been done to partition that variation. We completed a 4 × 4 diallel cross and Hayman analyses on several characteristics of these cries. The major result was the detection of directional dominance toward a higher rate of calling, longer calls, and calls of lower overall frequency with a greater bandwidth. Within the context of biometrical genetic theory, we conclude that calls with such characteristics may have important fitness value. Extending this idea, we propose that within the population sampled for this study (the animals of the four inbred strains and 12 F1 hybrid groups), the calls most effectively eliciting investigation and retrieval would be calls with the average hybrid values of the diallel cross.
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    Behavior genetics 25 (1995), S. 361-366 
    ISSN: 1573-3297
    Keywords: Mice ; aggression ; isolation-induced aggression ; predatory aggression ; selected lines ; genetic variation
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    Topics: Biology , Psychology
    Notes: Abstract Male mice differing in their genetically determined disposition for isolation-induced intermale aggression were compared on behaviors related to predatory aggression. An ongoing sequence of selective breeding established high-aggressive (Turku Aggressive: TA) and low-aggressive (Turku Non-Aggressive: TNA) lines from an outbred Swiss albino foundation stock. The parental strain, designated the Normal (N) strain, has been kept as a control line and is bred without regard to aggressiveness. Testing consisted of dropping a live cricket into the home cage of the individually housed experimental mice. Results showed that the TA males displayed shorter latencies to attack and spent more time in chasing, attacking, and consuming crickets than did TNA and N males. The TNA males displayed significantly less predatory aggression than both the TA and N males. When brothers of the males tested for predatory aggression were tested for intermale aggression, a similarly significant effect of breeding line was obtained for the latency to attack. Testing consisted of placing an intact male mouse into the cage of the male to be tested. The results suggest that there may be parallels in genetic variation between intermale and predatory attacking.
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  • 68
    ISSN: 1432-0878
    Keywords: Key words: Skeletal muscle ; Regeneration ; Ageing ; Strain-specific muscle precursor replication ; Autoradiography ; Mice ; BALBc (SJL/J)
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    Topics: Biology , Medicine
    Notes: Abstract. The patterns of skeletal muscle precursor cell replication after crush injury were compared by the use of autoradiographic techniques, in young (4-week-old) and old (39-week-old) BALBc and SJL/J mice. Similar comparisons were made between cut and crush lesions in old BALBc muscle. Muscle precursor cell replication commenced at 18–24 h after injury in both young and old muscles from both strains of mice. In young BALBc muscle the peak of myogenic activity at 60 h was 36 h earlier than in old mice. SJL/J muscle responded more rapidly than did BALBc: in young SJL/J the peak myogenic activity was at 46 h (14 h earlier than in young BALBc muscle), and in old SJL/J muscle the peak activity at 72 h was 24 h earlier than in old BALBc muscle. In all mice (both young and old) myogenic cell replication was substantially reduced by 120 h after injury. A comparison of the timing of muscle precursor cell replication in cut and crush lesions in old BALBc mice revealed a more rapid response in the cut lesion; this difference between the lesions is comparable with data from identical lesions in 6–8-week-old BALBc mice (McGeachie and Grounds 1987). However, the peak of myogenic replication in the older mice in the present study was some 26–36 h later than in the younger 6–8-week-old mice. These experiments show that, whilst muscle precursor cell replication commences at approximately the same time (about 24 h) after injury in young and old mice, the peak level of activity is delayed by some 24–36 h in old mice. In addition, the SJL/J mouse strain responds more rapidly and prolifically to muscle injury than does the BALBc strain.
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  • 69
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    Plant foods for human nutrition 45 (1994), S. 277-285 
    ISSN: 1573-9104
    Keywords: Bread ; Flour ; Fortification ; Iron ; Mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition
    Notes: Abstract Bread made from starch, unenriched, enriched, super-enriched and whole wheat flour was fed to male weanling mice for 21 days to explore the effect on iron utilization using liver, blood iron status and iron balance as parameters of evaluation. The results indicated that iron retentions, blood hemoglobin and hematocrit levels, and liver iron concentration numerically tended to be greater in mice fed super enriched bread than in mice fed the enriched bread but, for most parameters, these differences were not found to be statistically significant. Iron absorption from whole wheat bread was significantly poorer than the super enriched or enriched white wheat bread rations.
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  • 70
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    Parasitology research 61 (1980), S. 179-185 
    ISSN: 1432-1955
    Keywords: Trypanosoma cruzi ; Delayed hypersensitivity ; Mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Delayed type hypersensitivity reactions (DTH) to DNFB in C3H (susceptible) and (CBA×C57B1/10)F1 (resistant) mice were not impaired inTrypanosoma cruzi strain Y infections. Mice were infected IP with 100 parasites and sensitized or challenged 11 days after infection at the peak of parasitaemia. DTH reactions were found to be enhanced in C3H infected mice.
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  • 71
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    Parasitology research 61 (1980), S. 243-247 
    ISSN: 1432-1955
    Keywords: Hymenolepis microstoma ; Mice ; Orchiectomy ; Ovariectomy ; Growth
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Gonadectomy or sex of the host had no effect on the mean dry weight ofHymenolepis microstoma examined on day 12 postinfection (p.i.). However, on day 20 p.i. worms from intact or sham-operated male mice were significantly heavier than those recovered from the corresponding groups of female hosts. Orchiectomy of hosts lowered the average weight of these older worms, but ovariectomy had no effect.
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  • 72
    ISSN: 1432-1955
    Keywords: Trypanosoma cruzi ; Immunosuppression ; Immunenhancement ; Mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract (CBA×C57 B1/10)F1 mice infected intraperitoneally with 100 parasites ofTrypanosoma cruzi strain Y developed an infection with acute and chronic phases. Humoral suppression to sheep red blood cells was evident in both phases but enhancement of the response was achieved only at the beginning of the infection. A mitogen secreted by the parasite could explain both phenomenons.
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  • 73
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    Cell & tissue research 239 (1985), S. 375-382 
    ISSN: 1432-0878
    Keywords: B-lymphocytes ; Long-term bone marrow cultures ; Stromal cells ; Hemopoietic microenvironment ; Mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary A comparative morphological analysis of the Whitlock-Witte long-term B-cell culture and the predominantly myeloid Dexter long-term bone marrow culture demonstrates that similarities and differences exist between the two systems. Cells from the long-term B-cell cultures have a characteristic lymphoid morphology, whereas those from the Dexter cultures are predominantly granulocytes and macrophages along with a few undifferentiated blast cells. A multilayered stromal cell layer is a common feature of both systems. Scanning electron micrographs show the cells in this layer to be large, irregularly shaped and flattened. The data further indicate that there are unique features in the relationship between developing B cells and stromal cells in the long-term B-cell cultures. Large, mononuclear cells are present that have numerous membrane infoldings within which numerous lymphoid cells lie. The relationship of these cells to macrophages and epithelial/reticular cells is discussed.
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  • 74
    ISSN: 1432-0878
    Keywords: Afferent glomerular arteriole ; Renin ; Myosin ; Juxtaglomerular cells ; Tubulo-glomerular feedback ; Rats ; Mice
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    Topics: Biology , Medicine
    Notes: Summary The PAP-technique and antibodies to myosin were used to demonstrate the prerequisites for vasoconstriction in the juxtaglomerular part of the preglomerular arteriole as compared with its proximal segment in rats and mice. In contrast with the myosin-positive/renin-negative proximal part of the afferent arteriole no myosin-like activity could be demonstrated in its distal, renin-positive part. In accordance, no thick myofilaments were found in fully differentiated juxtaglomerular epithelioid cells replete with mature secretory granules. Stimulation of the renin-angiotensin system was followed by an increase of the reninpositive/myosin-negative portions of the preglomerular arteriole. Marked interspecies and internephron variations in the length of this vessel segment under control and stimulated conditions were observed. The juxtaglomerular part of the preglomerular arteriole close to the macula densa seems therefore to have only limited capabilities for vasoconstriction. This finding may be of importance regarding the tubulo-glomerular feedback, a mechanism allegedly triggered by the so-called ‘macula densa-signal’. It is suggested that this non-contractile segment of the afferent arteriole may represent the renal vascular receptor responsible for the increase of renin secretion during pressure reduction. Unlike the afferent arterioles, most of the efferent arterioles showed the highest level of their weak but distinct myosin-like immunoreactivity in the juxtaglomerular region, indicating some efferent juxtaglomerular vasoconstrictive ability.
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  • 75
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    Cell & tissue research 243 (1986), S. 65-68 
    ISSN: 1432-0878
    Keywords: Epithelial differentiation ; Stomach ; Duodenum ; Mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The response of adult epithelium in contact with heterologous mesenchymes/stromas was studied in three digestive organs (forestomach, glandular stomach, and duodenum). After various tissues were implanted beneath the epithelial layer of adult mice, the epithelial differentiation was examined after sacrifice of animals at intervals up to 24 weeks. In the forestomach and duodenum, the epithelial differentiation was not affected at all by the tissue implantation. In the glandular stomach, in contrast, epithelial cells exhibited altered differentiation in which chief and parietal cells disappeared and were replaced by columnar epithelial cells with PAS-positive granules. These epithelial cells often formed immature villi. Such differentiation-altered columnar epithelium (DACE) was induced by implanting any type of tissue and even by sham operation, indicating that it was induced by disorganization of the tissue-implanted stroma. The size of DACE was significantly influenced by the stage of implanted tissue; 14.5-day fetal mesenchyme induced the largest DACE, and was followed by 16.5-day fetal mesenchyme, adult stroma, and sham operation. These results suggest the importance of stromal organization in maintaining epithelial differentiation in the glandular stomach.
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    Cell & tissue research 238 (1984), S. 643-647 
    ISSN: 1432-0878
    Keywords: Binucleate cells ; Flow cytometry ; Hepatocytes ; Polyploidy pattern ; Mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Preparative and mathematical procedures are presented for the investigation of the ploidy pattern of liver cells. The DNA content of enzymatically-isolated liver cells and of nuclei was measured by flow cytometry. The true DNA content could not be measured directly due to superposition of statistical coincidences (demanding “first mode correction”) and incomplete separation of the nuclei in binucleate hepatocytes (demanding “second mode correction”). The statistical coincidences (caused by simultaneous measurement of two or more particles or subsequent reaggregation of particles) were corrected by splitting the “unnatural” i.e., aneuploid DNA content, and classifying it with the normal ploidy classes. In addition, the higher normal ploidy classes were reduced by the proportion of the measured coincidences in favour of the lower ones. The second mode correction applied to nuclear distributions only. It is a probability calculation based on counting nuclear pairs on microscope slides, and resulted in a 10% increase of diploid nuclei and a larger standard deviation between the age groups. 8c and 16c values were reduced. The tetraploid values were unchanged.
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    Cell & tissue research 221 (1981), S. 371-383 
    ISSN: 1432-0878
    Keywords: Catecholamines ; Chromaffin cells ; Nerve endings ; Adrenal gland ; Mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Light-microscopic autoradiography has revealed characteristic labelling patterns in adrenal medullary cells following the intravenous administration of different catecholamines. The uptake patterns for [3H] dopa, [3H] dopamine, [3H] noradrenaline and [3H] adrenaline have been compared. In all cases A cells were more active than NA cells and cells situated in the zone nearest the cortex demonstrated a markedly higher rate of uptake than central cells. It was concluded that adjacent chromaffin cells with very similar morphology may differ as much as 50 fold in their capacities to incorporate exogenous amines. The adrenergic nature of the innervation of the vessels of the adrenal cortex and capsule in the mouse was confirmed.
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  • 78
    ISSN: 1432-0878
    Keywords: 1,25(OH)2 vitamin D3 ; Testis ; Ductuli efferentes ; Sertoli cells ; Mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Evidence from results of autoradiographic studies in mice indicates that nuclei of Sertoli cells and of epithelial cells in the ductuli efferentes contain receptors for 1,25(OH)2 vitamin D3.
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  • 79
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    Cell & tissue research 245 (1986), S. 183-188 
    ISSN: 1432-0878
    Keywords: Spleen ; Lymph nodes ; Mice ; Cyclophosphamide ; Levan ; Light microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Morphological changes in spleen and lymph nodes of C57B1 mice induced by the cytotoxic agent cyclophosphamide and the polysaccharide levan, separately and in combination were studied. In the spleen, an early decrease (phase 1) and a late increase (phase 2) in weight were found to result from all drug administrations. The hypocellularity of phase 1 was due to a depletion in the white pulp affecting mainly the B-region. Splenic weight decrease was parallel to B-cell depletion and most marked in animals exposed to cyclophosphamide with levan. The splenomegaly observed during phase 2 with all treatments was due to extramedullary hematopoiesis in the red pulp. In the lymph nodes, administration of cyclophosphamide and levan produced opposite effects on the B-cell region: cyclophosphamide eliminated the germinal centers for 8 days, but levan seemed to enhance B-cell activity. In animals given both cyclophosphamide and levan, inhibition of B-cell activity began earlier than with cyclophosphamide alone. Levan does not antagonize the suppressive effect of cyclophosphamide on the B-cell component at the early phase when the drugs are given together.
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    Cell & tissue research 152 (1974), S. 525-542 
    ISSN: 1432-0878
    Keywords: Nidation ; Mice ; Cell interaction ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The interaction between the trophoblast and the maternal epithelium at early implantation was studied by means of light and electron microscopy. The uterine horns were fixed in situ and a double-embedding method was used to locate implantation sites. Observations were made on mice killed at 2 hour intervals 90–116 h. post coitum which covered the following stages: pre-attachment (i) with zona pellucida intact (ii) with zona pellucida in dissolution (iii) after loss of the zona; attachment; adherence; and invasion. The intact zona pellucida was electron opaque and of uniform density. In the stage of apparent dissolution it became electron dense and was trapped between trophoblast and epithelium. At preattachment the trophoblast cells were round. Subsequently they became long and attenuated, often with lysosomes in the cytoplasm proximal to the epithelial layer. Epithelial cells, which could be seen in various stages of degeneration were apparently phagocytosed by the trophoblast. Occasional pyknotic epithelial cells were seen, as well as some apparently normal ones which contained cytosegresomes. The possible reasons for their presence are discussed. The microvilli of the epithelial cells changed from regular and pointed at preattachment to short and irregular at adherence and invasion.
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    Cell & tissue research 152 (1974), S. 299-303 
    ISSN: 1432-0878
    Keywords: Post-capillary venules ; Mice ; Pathway of B lymphocytes ; Autoradiography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Histological observation on the mesenteric lymph node and Peyer's patches of C3H B mice, neonatally thymectomized, lethally irradiated and reconstituted with syngeneic bone marrow cells, showed that a large number of lymphocytes appeared selectively in the restricted territory surrounding the post-capillary venules. Severe depletion of lymphocytes persisted in most of the thymus-dependent areas. Lymphocytes were also observed passing through the walls of the post-capillary venules. Autoradiographic studies on the mesenteric lymph node of recipient B mice 30 minutes after intravenous injection of cells labelled with 3H-uridine and taken from lymph nodes of donor B mice showed that B lymphocytes could penetrate the walls of the post-capillary venules from the blood into the peripheral lymphoid tissues. The post-capillary venules, which are known as the recirculating route of T lymphocytes in normal animals, are thought to be the pathway of migrating B lymphocytes in B mice.
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  • 82
    ISSN: 1432-0878
    Keywords: Glucocorticoids ; Bone growth retardation ; Chondrocytes ; Rehabilitation ; Mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Immature A/J mice were treated for up to 7 weeks with intermittent doses of triamcinolone hexacetonide and were thereafter allowed to recover for 7 weeks. Qualitative and quantitative morphological measurements were performed on the epiphyseal cartilage plate and diaphyseal bone of the humerus. By the third injection significant structural changes were noted in the cartilaginous tissue followed by a complete cessation of bone growth. The hormonal inhibitory effect on long bone growth lasted throughout the experimental period. However, at the end of the recovery period the length of the humerus was 96% of the normal. In contrast, the humeral width at midshaft and the width of its medullary cavity revealed slower recovery, achieving only 80% of the control values. Following rehabilitation, the growth of experimental epiphyseal plates exceeded that of nontreated animals as their width and the number of hypertrophic chondrocytes were 131% and 125% of their controls respectively. Thus, in A/J mice (a highly susceptible inbred strain of mice) intermittent (every four days) administration of a long-acting corticosteroid hormone arrested endochondral and periosteal bone formation; the former, however, underwent full recovery following the termination of the hormonal treatment.
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    Cell & tissue research 246 (1986), S. 549-556 
    ISSN: 1432-0878
    Keywords: Submandibular gland ; Adrenal X zone ; Ovariectomy ; Morphometrical analysis ; Mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Morphological changes in submandibular glands of female mice following ovariectomy were studied morphometrically by light microscopy and ultrastructurally by electron microscopy. The X zone of the adrenal gland was examined in order to assess possible changes that might be expected to occur after ovariectomy. In submandibular glands, 1 to 4 weeks after ovariectomy, no changes were observed in percentages of the acinar, intercalated duct, and granular convoluted tubular areas occupying photomicrographs. However, an increase in the granular content of both intercalated duct and granular convoluted tubular cells was recognized. By contrast, the glandular picture 4 months after ovariectomy changed remarkably, resembling that of the male mouse both morphometrically and in terms of fine structure. In the adrenal cortex of control female mice, the X zone became thinner with aging. As compared with this, the X zone of ovariectomized mice at any time after the operation was thicker than that of controls. These observations suggest that the absence of ovarian hormones in the ovariectomized mouse may lead to prolonged functioning of X zone cells, which in turn may cause masculinization of the submandibular gland.
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  • 84
    Publication Date: 2010-04-13
    Description: Interleukin (IL)-17-producing helper T (T(H)17) cells are a distinct T-cell subset characterized by its pathological role in autoimmune diseases. IL-6 and transforming growth factor-beta (TGF-beta) induce T(H)17 development, in which the orphan nuclear receptors, RORgammat and RORalpha, have an indispensable role. However, in the absence of IL-6 and TGF-beta, the ectopic expression of RORgammat or RORalpha leads to only a modest IL-17 production. Here we identify a nuclear IkappaB family member, IkappaBzeta (encoded by the Nfkbiz gene), as a transcription factor required for T(H)17 development in mice. The ectopic expression of IkappaBzeta in naive CD4(+) T cells together with RORgammat or RORalpha potently induces T(H)17 development, even in the absence of IL-6 and TGF-beta. Notably, Nfkbiz(-/-) mice have a defect in T(H)17 development and a resistance to experimental autoimmune encephalomyelitis (EAE). The T-cell-intrinsic function of IkappaBzeta was clearly demonstrated by the resistance to EAE of the Rag2(-/-) mice into which Nfkbiz(-/-) CD4(+) T cells were transferred. In cooperation with RORgammat and RORalpha, IkappaBzeta enhances Il17a expression by binding directly to the regulatory region of the Il17a gene. This study provides evidence for the transcriptional mechanisms underlying T(H)17 development and points to a molecular basis for a novel therapeutic strategy against autoimmune disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Okamoto, Kazuo -- Iwai, Yoshiko -- Oh-Hora, Masatsugu -- Yamamoto, Masahiro -- Morio, Tomohiro -- Aoki, Kazuhiro -- Ohya, Keiichi -- Jetten, Anton M -- Akira, Shizuo -- Muta, Tatsushi -- Takayanagi, Hiroshi -- Z01-ES-101586/ES/NIEHS NIH HHS/ -- Intramural NIH HHS/ -- England -- Nature. 2010 Apr 29;464(7293):1381-5. doi: 10.1038/nature08922. Epub 2010 Apr 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell Signaling, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20383124" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing ; Animals ; Coculture Techniques ; Dendritic Cells/cytology/immunology ; Encephalomyelitis, Autoimmune, Experimental/metabolism ; *Gene Expression Regulation ; Interleukin-17/biosynthesis/genetics/*metabolism ; Mice ; NF-kappa B p50 Subunit/metabolism ; Nuclear Proteins/deficiency/genetics/*metabolism ; Nuclear Receptor Subfamily 1, Group F, Member 1/genetics/*metabolism ; Nuclear Receptor Subfamily 1, Group F, Member 3/genetics/*metabolism ; Promoter Regions, Genetic/genetics ; T-Lymphocytes, Helper-Inducer/*cytology/*metabolism ; Transcription, Genetic
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    Publication Date: 2010-07-20
    Description: DNA methylation is one of the best-characterized epigenetic modifications. Although the enzymes that catalyse DNA methylation have been characterized, enzymes responsible for demethylation have been elusive. A recent study indicates that the human TET1 protein could catalyse the conversion of 5-methylcytosine (5mC) of DNA to 5-hydroxymethylcytosine (5hmC), raising the possibility that DNA demethylation may be a Tet1-mediated process. Here we extend this study by demonstrating that all three mouse Tet proteins (Tet1, Tet2 and Tet3) can also catalyse a similar reaction. Tet1 has an important role in mouse embryonic stem (ES) cell maintenance through maintaining the expression of Nanog in ES cells. Downregulation of Nanog via Tet1 knockdown correlates with methylation of the Nanog promoter, supporting a role for Tet1 in regulating DNA methylation status. Furthermore, knockdown of Tet1 in pre-implantation embryos results in a bias towards trophectoderm differentiation. Thus, our studies not only uncover the enzymatic activity of the Tet proteins, but also demonstrate a role for Tet1 in ES cell maintenance and inner cell mass cell specification.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3491567/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3491567/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ito, Shinsuke -- D'Alessio, Ana C -- Taranova, Olena V -- Hong, Kwonho -- Sowers, Lawrence C -- Zhang, Yi -- CA084487/CA/NCI NIH HHS/ -- GM68804/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Aug 26;466(7310):1129-33. doi: 10.1038/nature09303.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20639862" target="_blank"〉PubMed〈/a〉
    Keywords: 5-Methylcytosine/*metabolism ; Alkaline Phosphatase/metabolism ; Animals ; Blastocyst Inner Cell Mass/*metabolism ; Cell Proliferation ; Cytosine/*analogs & derivatives/metabolism ; DNA-Binding Proteins/genetics/*metabolism ; Embryonic Stem Cells/*cytology ; Gene Expression Regulation, Developmental ; Gene Knockdown Techniques ; Homeodomain Proteins/metabolism ; Mice ; Proto-Oncogene Proteins/genetics/*metabolism
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  • 86
    Publication Date: 2010-07-20
    Description: Chronic myelogenous leukaemia (CML) can progress from a slow growing chronic phase to an aggressive blast crisis phase, but the molecular basis of this transition remains poorly understood. Here we have used mouse models of CML to show that disease progression is regulated by the Musashi-Numb signalling axis. Specifically, we find that the chronic phase is marked by high levels of Numb expression whereas the blast crisis phase has low levels of Numb expression, and that ectopic expression of Numb promotes differentiation and impairs advanced-phase disease in vivo. As a possible explanation for the decreased levels of Numb in the blast crisis phase, we show that NUP98-HOXA9, an oncogene associated with blast crisis CML, can trigger expression of the RNA-binding protein Musashi2 (Msi2), which in turn represses Numb. Notably, loss of Msi2 restores Numb expression and significantly impairs the development and propagation of blast crisis CML in vitro and in vivo. Finally we show that Msi2 expression is not only highly upregulated during human CML progression but is also an early indicator of poorer prognosis. These data show that the Musashi-Numb pathway can control the differentiation of CML cells, and raise the possibility that targeting this pathway may provide a new strategy for the therapy of aggressive leukaemias.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2918284/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2918284/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ito, Takahiro -- Kwon, Hyog Young -- Zimdahl, Bryan -- Congdon, Kendra L -- Blum, Jordan -- Lento, William E -- Zhao, Chen -- Lagoo, Anand -- Gerrard, Gareth -- Foroni, Letizia -- Goldman, John -- Goh, Harriet -- Kim, Soo-Hyun -- Kim, Dong-Wook -- Chuah, Charles -- Oehler, Vivian G -- Radich, Jerald P -- Jordan, Craig T -- Reya, Tannishtha -- AI067798/AI/NIAID NIH HHS/ -- CA122206/CA/NCI NIH HHS/ -- CA140371/CA/NCI NIH HHS/ -- CA18029/CA/NCI NIH HHS/ -- DK072234/DK/NIDDK NIH HHS/ -- DK63031/DK/NIDDK NIH HHS/ -- DP1 CA174422/CA/NCI NIH HHS/ -- DP1 OD006430/OD/NIH HHS/ -- DP1 OD006430-01/OD/NIH HHS/ -- DP1 OD006430-02/OD/NIH HHS/ -- DP1OD006430/OD/NIH HHS/ -- HL097767/HL/NHLBI NIH HHS/ -- P01 CA018029/CA/NCI NIH HHS/ -- R01 CA140371/CA/NCI NIH HHS/ -- R01 DK063031/DK/NIDDK NIH HHS/ -- R01 DK063031-01/DK/NIDDK NIH HHS/ -- R01 DK063031-01S1/DK/NIDDK NIH HHS/ -- R01 DK063031-02/DK/NIDDK NIH HHS/ -- R01 DK063031-03/DK/NIDDK NIH HHS/ -- R01 DK063031-04/DK/NIDDK NIH HHS/ -- R01 DK063031-05/DK/NIDDK NIH HHS/ -- R01 DK063031-06/DK/NIDDK NIH HHS/ -- R01 DK063031-07/DK/NIDDK NIH HHS/ -- R01 DK063031-07S1/DK/NIDDK NIH HHS/ -- R01 DK063031-08/DK/NIDDK NIH HHS/ -- R01 DK072234/DK/NIDDK NIH HHS/ -- R01 DK072234-01A1/DK/NIDDK NIH HHS/ -- R01 DK072234-02/DK/NIDDK NIH HHS/ -- R01 DK072234-03/DK/NIDDK NIH HHS/ -- R01 DK072234-04/DK/NIDDK NIH HHS/ -- R01 HL097767/HL/NHLBI NIH HHS/ -- R01 HL097767-01/HL/NHLBI NIH HHS/ -- R01 HL097767-02/HL/NHLBI NIH HHS/ -- T32 GM007184-33/GM/NIGMS NIH HHS/ -- U19 AI067798/AI/NIAID NIH HHS/ -- U19 AI067798-010006/AI/NIAID NIH HHS/ -- U19 AI067798-020006/AI/NIAID NIH HHS/ -- U19 AI067798-030006/AI/NIAID NIH HHS/ -- U19 AI067798-040006/AI/NIAID NIH HHS/ -- U19 AI067798-050006/AI/NIAID NIH HHS/ -- England -- Nature. 2010 Aug 5;466(7307):765-8. doi: 10.1038/nature09171. Epub 2010 Jul 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20639863" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blast Crisis/genetics/metabolism/pathology ; *Cell Differentiation/genetics ; Disease Progression ; Fusion Proteins, bcr-abl/genetics/metabolism ; Gene Expression Regulation, Neoplastic ; Homeodomain Proteins/genetics/metabolism ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics/*metabolism/*pathology ; Membrane Proteins/biosynthesis/genetics/metabolism ; Mice ; Mice, Inbred C57BL ; Nerve Tissue Proteins/biosynthesis/genetics/metabolism ; Nuclear Pore Complex Proteins/genetics/metabolism ; Oncogene Proteins, Fusion/genetics/metabolism ; Prognosis ; RNA-Binding Proteins/biosynthesis/genetics/*metabolism ; Receptor, Notch1/metabolism ; Signal Transduction ; Tumor Suppressor Protein p53/metabolism ; Up-Regulation
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  • 87
    Publication Date: 2010-05-14
    Description: The main reason why tumours are not controlled by the immune system is that, unlike pathogens, they do not express potent tumour rejection antigens (TRAs). Tumour vaccination aims at stimulating a systemic immune response targeted to, mostly weak, antigens expressed in the disseminated tumour lesions. Main challenges in developing effective vaccination protocols are the identification of potent and broadly expressed TRAs and effective adjuvants to stimulate a robust and durable immune response. Here we describe an alternative approach in which the expression of new, and thereby potent, antigens are induced in tumour cells by inhibiting nonsense-mediated messenger RNA decay (NMD). Small interfering RNA (siRNA)-mediated inhibition of NMD in tumour cells led to the expression of new antigenic determinants and their immune-mediated rejection. In subcutaneous and metastatic tumour models, tumour-targeted delivery of NMD factor-specific siRNAs conjugated to oligonucleotide aptamer ligands led to significant inhibition of tumour growth that was superior to that of vaccination with granulocyte-macrophage colony-stimulating factor (GM-CSF)-expressing irradiated tumour cells, and could be further enhanced by co-stimulation. Tumour-targeted NMD inhibition forms the basis of a simple, broadly useful, and clinically feasible approach to enhance the antigenicity of disseminated tumours leading to their immune recognition and rejection. The cell-free chemically synthesized oligonucleotide backbone of aptamer-siRNAs reduces the risk of immunogenicity and enhances the feasibility of generating reagents suitable for clinical use.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3107067/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3107067/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pastor, Fernando -- Kolonias, Despina -- Giangrande, Paloma H -- Gilboa, Eli -- R01 CA138503/CA/NCI NIH HHS/ -- R01 CA151857-02/CA/NCI NIH HHS/ -- England -- Nature. 2010 May 13;465(7295):227-30. doi: 10.1038/nature08999.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology & Immunology, Dodson Interdisciplinary Immunotherapy Institute, University of Miami Miller School of Medicine Miami, Florida 33134, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20463739" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, Neoplasm/*genetics/*immunology ; Aptamers, Nucleotide/genetics ; Cancer Vaccines/genetics/immunology/metabolism ; Carrier Proteins/genetics ; Cell Line, Tumor ; Chickens/genetics ; Colonic Neoplasms/*genetics/*immunology/pathology ; Gene Expression Regulation, Neoplastic ; Granulocyte-Macrophage Colony-Stimulating Factor/genetics/metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Nude ; Neoplasm Transplantation ; RNA Interference ; RNA Stability/*genetics ; RNA, Small Interfering/*genetics/therapeutic use ; Xenograft Model Antitumor Assays
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 88
    Publication Date: 2010-12-03
    Description: The capacity to fine-tune cellular bioenergetics with the demands of stem-cell maintenance and regeneration is central to normal development and ageing, and to organismal survival during periods of acute stress. How energy metabolism and stem-cell homeostatic processes are coordinated is not well understood. Lkb1 acts as an evolutionarily conserved regulator of cellular energy metabolism in eukaryotic cells and functions as the major upstream kinase to phosphorylate AMP-activated protein kinase (AMPK) and 12 other AMPK-related kinases. Whether Lkb1 regulates stem-cell maintenance remains unknown. Here we show that Lkb1 has an essential role in haematopoietic stem cell (HSC) homeostasis. We demonstrate that ablation of Lkb1 in adult mice results in severe pancytopenia and subsequent lethality. Loss of Lkb1 leads to impaired survival and escape from quiescence of HSCs, resulting in exhaustion of the HSC pool and a marked reduction of HSC repopulating potential in vivo. Lkb1 deletion has an impact on cell proliferation in HSCs, but not on more committed compartments, pointing to context-specific functions for Lkb1 in haematopoiesis. The adverse impact of Lkb1 deletion on haematopoiesis was predominantly cell-autonomous and mTOR complex 1 (mTORC1)-independent, and involves multiple mechanisms converging on mitochondrial apoptosis and possibly downregulation of PGC-1 coactivators and their transcriptional network, which have critical roles in mitochondrial biogenesis and function. Thus, Lkb1 serves as an essential regulator of HSCs and haematopoiesis, and more generally, points to the critical importance of coupling energy metabolism and stem-cell homeostasis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3058342/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3058342/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gan, Boyi -- Hu, Jian -- Jiang, Shan -- Liu, Yingchun -- Sahin, Ergun -- Zhuang, Li -- Fletcher-Sananikone, Eliot -- Colla, Simona -- Wang, Y Alan -- Chin, Lynda -- Depinho, Ronald A -- 01CA141508/CA/NCI NIH HHS/ -- R21 CA135057/CA/NCI NIH HHS/ -- R21 CA135057-01/CA/NCI NIH HHS/ -- R21CA135057/CA/NCI NIH HHS/ -- U01 CA141508/CA/NCI NIH HHS/ -- U01 CA141508-01/CA/NCI NIH HHS/ -- England -- Nature. 2010 Dec 2;468(7324):701-4. doi: 10.1038/nature09595.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Belfer Institute for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21124456" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis ; Cell Cycle/*physiology ; Cell Proliferation ; Cell Survival ; *Energy Metabolism ; Female ; Gene Deletion ; Hematopoiesis ; Hematopoietic Stem Cells/*cytology/*metabolism/pathology ; *Homeostasis ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mitochondria/metabolism/pathology ; Multiprotein Complexes ; Pancytopenia/genetics ; Phenotype ; Protein-Serine-Threonine Kinases/deficiency/genetics/*metabolism ; Proteins/metabolism ; Survival Analysis ; TOR Serine-Threonine Kinases ; Transcription Factors/metabolism
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  • 89
    Publication Date: 2010-01-19
    Description: Influenza A virus, being responsible for seasonal epidemics and reoccurring pandemics, represents a worldwide threat to public health. High mutation rates facilitate the generation of viral escape mutants, rendering vaccines and drugs directed against virus-encoded targets potentially ineffective. In contrast, targeting host cell determinants temporarily dispensable for the host but crucial for virus replication could prevent viral escape. Here we report the discovery of 287 human host cell genes influencing influenza A virus replication in a genome-wide RNA interference (RNAi) screen. Using an independent assay we confirmed 168 hits (59%) inhibiting either the endemic H1N1 (119 hits) or the current pandemic swine-origin (121 hits) influenza A virus strains, with an overlap of 60%. Notably, a subset of these common hits was also essential for replication of a highly pathogenic avian H5N1 strain. In-depth analyses of several factors provided insights into their infection stage relevance. Notably, SON DNA binding protein (SON) was found to be important for normal trafficking of influenza virions to late endosomes early in infection. We also show that a small molecule inhibitor of CDC-like kinase 1 (CLK1) reduces influenza virus replication by more than two orders of magnitude, an effect connected with impaired splicing of the viral M2 messenger RNA. Furthermore, influenza-virus-infected p27(-/-) (cyclin-dependent kinase inhibitor 1B; Cdkn1b) mice accumulated significantly lower viral titres in the lung, providing in vivo evidence for the importance of this gene. Thus, our results highlight the potency of genome-wide RNAi screening for the dissection of virus-host interactions and the identification of drug targets for a broad range of influenza viruses.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Karlas, Alexander -- Machuy, Nikolaus -- Shin, Yujin -- Pleissner, Klaus-Peter -- Artarini, Anita -- Heuer, Dagmar -- Becker, Daniel -- Khalil, Hany -- Ogilvie, Lesley A -- Hess, Simone -- Maurer, Andre P -- Muller, Elke -- Wolff, Thorsten -- Rudel, Thomas -- Meyer, Thomas F -- England -- Nature. 2010 Feb 11;463(7282):818-22. doi: 10.1038/nature08760. Epub 2010 Jan 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Biology Department, Max Planck Institute for Infection Biology, Chariteplatz 1, 10117 Berlin, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20081832" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Factors/genetics/metabolism ; Cell Line ; Cells, Cultured ; Chick Embryo ; Cyclin-Dependent Kinase Inhibitor p27/deficiency/genetics/metabolism ; Epithelial Cells/virology ; Genome, Human/genetics ; *Host-Pathogen Interactions/genetics/physiology ; Humans ; Influenza A Virus, H1N1 Subtype/classification/*growth & development ; Influenza, Human/*genetics/*virology ; Lung/cytology ; Mice ; Mice, Inbred C57BL ; Protein-Serine-Threonine Kinases/genetics ; Protein-Tyrosine Kinases/genetics ; *RNA Interference ; Virus Replication/*physiology
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  • 90
    facet.materialart.
    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2010-06-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lydon, John P -- England -- Nature. 2010 Jun 10;465(7299):695-6. doi: 10.1038/465695a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20535190" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Breast Neoplasms/pathology ; Cell Division ; Estrogens/*metabolism ; Estrous Cycle/physiology ; Female ; Humans ; Lactation/physiology ; Mammary Glands, Animal/*cytology ; Mice ; Paracrine Communication ; Pregnancy ; Pregnancy, Animal/physiology ; Progesterone/*metabolism ; RANK Ligand/metabolism ; Receptors, Estrogen/deficiency ; Receptors, Progesterone/deficiency ; Stem Cell Niche/cytology/metabolism ; Stem Cells/*cytology/drug effects/*metabolism
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  • 91
    Publication Date: 2010-02-25
    Description: Tumours with mutant BRAF are dependent on the RAF-MEK-ERK signalling pathway for their growth. We found that ATP-competitive RAF inhibitors inhibit ERK signalling in cells with mutant BRAF, but unexpectedly enhance signalling in cells with wild-type BRAF. Here we demonstrate the mechanistic basis for these findings. We used chemical genetic methods to show that drug-mediated transactivation of RAF dimers is responsible for paradoxical activation of the enzyme by inhibitors. Induction of ERK signalling requires direct binding of the drug to the ATP-binding site of one kinase of the dimer and is dependent on RAS activity. Drug binding to one member of RAF homodimers (CRAF-CRAF) or heterodimers (CRAF-BRAF) inhibits one protomer, but results in transactivation of the drug-free protomer. In BRAF(V600E) tumours, RAS is not activated, thus transactivation is minimal and ERK signalling is inhibited in cells exposed to RAF inhibitors. These results indicate that RAF inhibitors will be effective in tumours in which BRAF is mutated. Furthermore, because RAF inhibitors do not inhibit ERK signalling in other cells, the model predicts that they would have a higher therapeutic index and greater antitumour activity than mitogen-activated protein kinase (MEK) inhibitors, but could also cause toxicity due to MEK/ERK activation. These predictions have been borne out in a recent clinical trial of the RAF inhibitor PLX4032 (refs 4, 5). The model indicates that promotion of RAF dimerization by elevation of wild-type RAF expression or RAS activity could lead to drug resistance in mutant BRAF tumours. In agreement with this prediction, RAF inhibitors do not inhibit ERK signalling in cells that coexpress BRAF(V600E) and mutant RAS.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3178447/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3178447/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Poulikakos, Poulikos I -- Zhang, Chao -- Bollag, Gideon -- Shokat, Kevan M -- Rosen, Neal -- 1P01CA129243-02/CA/NCI NIH HHS/ -- 2R01EB001987/EB/NIBIB NIH HHS/ -- P01 CA129243-010002/CA/NCI NIH HHS/ -- R01 EB001987/EB/NIBIB NIH HHS/ -- U01 CA091178/CA/NCI NIH HHS/ -- U01 CA091178-01/CA/NCI NIH HHS/ -- England -- Nature. 2010 Mar 18;464(7287):427-30. doi: 10.1038/nature08902.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Molecular Pharmacology and Chemistry and Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20179705" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Animals ; Catalytic Domain ; Cell Line ; Cell Line, Tumor ; Enzyme Activation/drug effects ; Extracellular Signal-Regulated MAP Kinases/*metabolism ; Humans ; Indoles/pharmacology ; MAP Kinase Signaling System/*drug effects ; Mice ; Mitogen-Activated Protein Kinase Kinases/metabolism ; Models, Biological ; Neoplasms/drug therapy/enzymology/genetics/metabolism ; Phosphorylation ; Protein Binding ; Protein Kinase Inhibitors/metabolism/*pharmacology/therapeutic use ; Protein Multimerization ; Proto-Oncogene Proteins B-raf/antagonists & ; inhibitors/chemistry/genetics/*metabolism ; Sulfonamides/pharmacology ; Transcriptional Activation/*drug effects ; raf Kinases/*antagonists & inhibitors/chemistry/genetics/*metabolism ; ras Proteins/genetics/metabolism
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  • 92
    facet.materialart.
    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2010-05-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2010 May 20;465(7296):267. doi: 10.1038/465267a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20485389" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Rights/trends ; Animals ; Animals, Laboratory/anatomy & histology/physiology ; Cognition/*physiology ; Empathy/physiology ; Humans ; Mice ; *Models, Animal ; Neurosciences/*methods/trends ; Prefrontal Cortex/anatomy & histology/physiology ; Primates/*anatomy & histology/*physiology ; Rats
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  • 93
    Publication Date: 2010-06-22
    Description: The molecular clock maintains energy constancy by producing circadian oscillations of rate-limiting enzymes involved in tissue metabolism across the day and night. During periods of feeding, pancreatic islets secrete insulin to maintain glucose homeostasis, and although rhythmic control of insulin release is recognized to be dysregulated in humans with diabetes, it is not known how the circadian clock may affect this process. Here we show that pancreatic islets possess self-sustained circadian gene and protein oscillations of the transcription factors CLOCK and BMAL1. The phase of oscillation of islet genes involved in growth, glucose metabolism and insulin signalling is delayed in circadian mutant mice, and both Clock and Bmal1 (also called Arntl) mutants show impaired glucose tolerance, reduced insulin secretion and defects in size and proliferation of pancreatic islets that worsen with age. Clock disruption leads to transcriptome-wide alterations in the expression of islet genes involved in growth, survival and synaptic vesicle assembly. Notably, conditional ablation of the pancreatic clock causes diabetes mellitus due to defective beta-cell function at the very latest stage of stimulus-secretion coupling. These results demonstrate a role for the beta-cell clock in coordinating insulin secretion with the sleep-wake cycle, and reveal that ablation of the pancreatic clock can trigger the onset of diabetes mellitus.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2920067/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2920067/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marcheva, Biliana -- Ramsey, Kathryn Moynihan -- Buhr, Ethan D -- Kobayashi, Yumiko -- Su, Hong -- Ko, Caroline H -- Ivanova, Ganka -- Omura, Chiaki -- Mo, Shelley -- Vitaterna, Martha H -- Lopez, James P -- Philipson, Louis H -- Bradfield, Christopher A -- Crosby, Seth D -- JeBailey, Lellean -- Wang, Xiaozhong -- Takahashi, Joseph S -- Bass, Joseph -- P01 AG011412/AG/NIA NIH HHS/ -- P01 AG011412-080011/AG/NIA NIH HHS/ -- R01 HL097817/HL/NHLBI NIH HHS/ -- R01 HL097817-01/HL/NHLBI NIH HHS/ -- R37 ES005703/ES/NIEHS NIH HHS/ -- R37-ES-005703/ES/NIEHS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Jul 29;466(7306):627-31. doi: 10.1038/nature09253.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20562852" target="_blank"〉PubMed〈/a〉
    Keywords: ARNTL Transcription Factors/deficiency/*genetics/metabolism ; Aging/genetics/pathology ; Animals ; Blood Glucose/analysis/metabolism ; CLOCK Proteins/deficiency/*genetics/metabolism ; Cell Proliferation ; Cell Size ; Cell Survival ; Circadian Rhythm/genetics/*physiology ; Diabetes Mellitus/genetics/*metabolism ; Gene Expression Profiling ; Glucose Intolerance/genetics ; Glucose Tolerance Test ; In Vitro Techniques ; Insulin/*blood/metabolism/secretion ; Islets of Langerhans/*metabolism/pathology/secretion ; Mice ; Period Circadian Proteins/genetics/metabolism ; Phenotype ; Sleep/genetics/physiology ; Synaptic Vesicles/metabolism ; Wakefulness/genetics/physiology
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  • 94
    Publication Date: 2010-01-29
    Description: Cellular differentiation and lineage commitment are considered to be robust and irreversible processes during development. Recent work has shown that mouse and human fibroblasts can be reprogrammed to a pluripotent state with a combination of four transcription factors. This raised the question of whether transcription factors could directly induce other defined somatic cell fates, and not only an undifferentiated state. We hypothesized that combinatorial expression of neural-lineage-specific transcription factors could directly convert fibroblasts into neurons. Starting from a pool of nineteen candidate genes, we identified a combination of only three factors, Ascl1, Brn2 (also called Pou3f2) and Myt1l, that suffice to rapidly and efficiently convert mouse embryonic and postnatal fibroblasts into functional neurons in vitro. These induced neuronal (iN) cells express multiple neuron-specific proteins, generate action potentials and form functional synapses. Generation of iN cells from non-neural lineages could have important implications for studies of neural development, neurological disease modelling and regenerative medicine.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2829121/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2829121/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vierbuchen, Thomas -- Ostermeier, Austin -- Pang, Zhiping P -- Kokubu, Yuko -- Sudhof, Thomas C -- Wernig, Marius -- 1018438-142-PABCA/PHS HHS/ -- 5T32NS007280/NS/NINDS NIH HHS/ -- T32 CA009302/CA/NCI NIH HHS/ -- U01 HL100397/HL/NHLBI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Feb 25;463(7284):1035-41. doi: 10.1038/nature08797. Epub 2010 Jan 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Stem Cell Biology and Regenerative Medicine, Department of Pathology, Stanford University School of Medicine, 1050 Arastradero Road, Palo Alto, California 94304, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20107439" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics/metabolism ; Biomarkers/analysis ; Cell Line ; *Cell Lineage ; *Cell Transdifferentiation ; Cells, Cultured ; Embryo, Mammalian/cytology ; Fibroblasts/*cytology ; Mice ; Nerve Tissue Proteins/genetics/metabolism ; Neurons/*cytology/metabolism/*physiology ; POU Domain Factors/genetics/metabolism ; Regenerative Medicine ; Synapses/metabolism ; Tail/cytology ; Time Factors ; Transcription Factors/genetics/metabolism
    Print ISSN: 0028-0836
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 95
    Publication Date: 2010-01-08
    Description: The ability to silence the activity of genetically specified neurons in a temporally precise fashion would provide the opportunity to investigate the causal role of specific cell classes in neural computations, behaviours and pathologies. Here we show that members of the class of light-driven outward proton pumps can mediate powerful, safe, multiple-colour silencing of neural activity. The gene archaerhodopsin-3 (Arch) from Halorubrum sodomense enables near-100% silencing of neurons in the awake brain when virally expressed in the mouse cortex and illuminated with yellow light. Arch mediates currents of several hundred picoamps at low light powers, and supports neural silencing currents approaching 900 pA at light powers easily achievable in vivo. Furthermore, Arch spontaneously recovers from light-dependent inactivation, unlike light-driven chloride pumps that enter long-lasting inactive states in response to light. These properties of Arch are appropriate to mediate the optical silencing of significant brain volumes over behaviourally relevant timescales. Arch function in neurons is well tolerated because pH excursions created by Arch illumination are minimized by self-limiting mechanisms to levels comparable to those mediated by channelrhodopsins or natural spike firing. To highlight how proton pump ecological and genomic diversity may support new innovation, we show that the blue-green light-drivable proton pump from the fungus Leptosphaeria maculans (Mac) can, when expressed in neurons, enable neural silencing by blue light, thus enabling alongside other developed reagents the potential for independent silencing of two neural populations by blue versus red light. Light-driven proton pumps thus represent a high-performance and extremely versatile class of 'optogenetic' voltage and ion modulator, which will broadly enable new neuroscientific, biological, neurological and psychiatric investigations.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939492/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2939492/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chow, Brian Y -- Han, Xue -- Dobry, Allison S -- Qian, Xiaofeng -- Chuong, Amy S -- Li, Mingjie -- Henninger, Michael A -- Belfort, Gabriel M -- Lin, Yingxi -- Monahan, Patrick E -- Boyden, Edward S -- 1K99MH085944/MH/NIMH NIH HHS/ -- DP2 OD002002/OD/NIH HHS/ -- DP2 OD002002-01/OD/NIH HHS/ -- K99 MH085944/MH/NIMH NIH HHS/ -- K99 MH085944-01/MH/NIMH NIH HHS/ -- England -- Nature. 2010 Jan 7;463(7277):98-102. doi: 10.1038/nature08652.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The MIT Media Laboratory, Synthetic Neurobiology Group, and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20054397" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials/radiation effects ; Animals ; Ascomycota/metabolism/radiation effects ; Color ; Electric Conductivity ; Euryarchaeota/metabolism/radiation effects ; Genetic Engineering/*methods ; Hydrogen-Ion Concentration ; Mice ; Molecular Sequence Data ; Neocortex/cytology/physiology/radiation effects ; Neurons/*metabolism/*radiation effects ; Proton Pumps/classification/genetics/*metabolism/*radiation effects ; Rhodopsins, Microbial/antagonists & inhibitors/genetics/metabolism/radiation ; effects ; Wakefulness
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 96
    Publication Date: 2010-08-06
    Description: Long interspersed element-1 (LINE-1 or L1) retrotransposition continues to affect human genome evolution. L1s can retrotranspose in the germline, during early development and in select somatic cells; however, the host response to L1 retrotransposition remains largely unexplored. Here we show that reporter genes introduced into the genome of various human embryonic carcinoma-derived cell lines (ECs) by L1 retrotransposition are rapidly and efficiently silenced either during or immediately after their integration. Treating ECs with histone deacetylase inhibitors rapidly reverses this silencing, and chromatin immunoprecipitation experiments revealed that reactivation of the reporter gene was correlated with changes in chromatin status at the L1 integration site. Under our assay conditions, rapid silencing was also observed when reporter genes were delivered into ECs by mouse L1s and a zebrafish LINE-2 element, but not when similar reporter genes were delivered into ECs by Moloney murine leukaemia virus or human immunodeficiency virus, suggesting that these integration events are silenced by distinct mechanisms. Finally, we demonstrate that subjecting ECs to culture conditions that promote differentiation attenuates the silencing of reporter genes delivered by L1 retrotransposition, but that differentiation, in itself, is not sufficient to reactivate previously silenced reporter genes. Thus, our data indicate that ECs differ from many differentiated cells in their ability to silence reporter genes delivered by L1 retrotransposition.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3034402/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3034402/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Garcia-Perez, Jose L -- Morell, Maria -- Scheys, Joshua O -- Kulpa, Deanna A -- Morell, Santiago -- Carter, Christoph C -- Hammer, Gary D -- Collins, Kathleen L -- O'Shea, K Sue -- Menendez, Pablo -- Moran, John V -- 5 P30 CA46592/CA/NCI NIH HHS/ -- GM-069985/GM/NIGMS NIH HHS/ -- GM060518/GM/NIGMS NIH HHS/ -- GM082970/GM/NIGMS NIH HHS/ -- NS-048187/NS/NINDS NIH HHS/ -- R01 DK62027/DK/NIDDK NIH HHS/ -- R01 GM060518/GM/NIGMS NIH HHS/ -- R01 GM060518-12/GM/NIGMS NIH HHS/ -- R01 GM082970/GM/NIGMS NIH HHS/ -- R01 GM082970-04/GM/NIGMS NIH HHS/ -- R01AI051198/AI/NIAID NIH HHS/ -- T32-GM08322/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Aug 5;466(7307):769-73. doi: 10.1038/nature09209.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Human Genetics, 1241 East Catherine Street, University of Michigan Medical School, Ann Arbor, Michigan 48109-5618, USA. josel.garcia.perez@juntadeandalucia.es〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20686575" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Differentiation/genetics/physiology ; Cell Line, Tumor ; Chromatin/drug effects/genetics/metabolism ; Chromatin Immunoprecipitation ; Embryonal Carcinoma Stem Cells/*metabolism/pathology ; Epigenesis, Genetic/drug effects/*genetics ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; *Gene Silencing/drug effects ; Genes, Reporter/genetics ; Genetic Engineering ; Genetic Vectors/genetics ; Genome, Human/genetics ; HIV/genetics ; Histone Deacetylase Inhibitors/pharmacology ; Humans ; Long Interspersed Nucleotide Elements/genetics ; Male ; Mice ; Models, Genetic ; Moloney murine leukemia virus/genetics ; Retroelements/*genetics ; Zebrafish/genetics
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 97
    Publication Date: 2010-10-01
    Description: Breast cancer is one of the most common cancers in humans and will on average affect up to one in eight women in their lifetime in the United States and Europe. The Women's Health Initiative and the Million Women Study have shown that hormone replacement therapy is associated with an increased risk of incident and fatal breast cancer. In particular, synthetic progesterone derivatives (progestins) such as medroxyprogesterone acetate (MPA), used in millions of women for hormone replacement therapy and contraceptives, markedly increase the risk of developing breast cancer. Here we show that the in vivo administration of MPA triggers massive induction of the key osteoclast differentiation factor RANKL (receptor activator of NF-kappaB ligand) in mammary-gland epithelial cells. Genetic inactivation of the RANKL receptor RANK in mammary-gland epithelial cells prevents MPA-induced epithelial proliferation, impairs expansion of the CD49f(hi) stem-cell-enriched population, and sensitizes these cells to DNA-damage-induced cell death. Deletion of RANK from the mammary epithelium results in a markedly decreased incidence and delayed onset of MPA-driven mammary cancer. These data show that the RANKL/RANK system controls the incidence and onset of progestin-driven breast cancer.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084017/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084017/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schramek, Daniel -- Leibbrandt, Andreas -- Sigl, Verena -- Kenner, Lukas -- Pospisilik, John A -- Lee, Heather J -- Hanada, Reiko -- Joshi, Purna A -- Aliprantis, Antonios -- Glimcher, Laurie -- Pasparakis, Manolis -- Khokha, Rama -- Ormandy, Christopher J -- Widschwendter, Martin -- Schett, Georg -- Penninger, Josef M -- HD055601/HD/NICHD NIH HHS/ -- R01 HD055601/HD/NICHD NIH HHS/ -- R01 HD055601-04/HD/NICHD NIH HHS/ -- England -- Nature. 2010 Nov 4;468(7320):98-102. doi: 10.1038/nature09387. Epub 2010 Sep 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, 1030 Vienna, Austria.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20881962" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis/radiation effects ; Cell Differentiation ; Cell Proliferation/drug effects ; DNA Damage ; Epithelial Cells/cytology/drug effects/metabolism/radiation effects ; Female ; Gamma Rays ; Integrin alpha6/metabolism ; Mammary Neoplasms, Experimental/*chemically ; induced/genetics/metabolism/*pathology ; Medroxyprogesterone Acetate/administration & dosage/adverse effects ; Mice ; NF-kappa B/metabolism ; Osteoclasts/cytology ; Phosphoproteins/analysis/immunology ; Progestins/administration & dosage/*adverse effects ; RANK Ligand/deficiency/genetics/*metabolism ; Receptor Activator of Nuclear Factor-kappa B/deficiency/genetics/metabolism ; Signal Transduction ; Stem Cells/cytology/drug effects/metabolism
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 98
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    Nature Publishing Group (NPG)
    Publication Date: 2010-07-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kher, Unmesh -- England -- Nature. 2010 Jul 15;466(7304):S21-2. doi: 10.1038/nature09245.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉International AIDS Vaccine Initiative.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20631702" target="_blank"〉PubMed〈/a〉
    Keywords: AIDS Vaccines ; Allergy and Immunology ; Animals ; Anti-HIV Agents/administration & dosage/supply & distribution/therapeutic use ; Biomedical Research/economics/manpower/*organization & administration/trends ; Computational Biology ; Disease Progression ; Drug Combinations ; Financing, Organized/economics ; HIV/drug effects/enzymology/genetics/isolation & purification ; HIV Infections/drug therapy/immunology/*therapy/virology ; Humans ; *Interdisciplinary Communication ; Mice ; Models, Animal ; Research Personnel/*organization & administration/trends ; Research Support as Topic/economics/organization & administration ; Systems Biology ; Treatment Outcome ; Viral Load
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 99
    facet.materialart.
    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2010-05-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Green, Douglas R -- England -- Nature. 2010 May 27;465(7297):433. doi: 10.1038/465433a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20505719" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD95/deficiency/genetics/*metabolism ; Apoptosis ; Autocrine Communication ; Cell Proliferation ; Enzyme Activation ; Fas Ligand Protein/deficiency/metabolism ; Humans ; Inflammation/metabolism ; JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism ; Mice ; Neoplasms/*metabolism/*pathology ; Phosphatidylinositol 3-Kinases/metabolism ; Proto-Oncogene Proteins c-akt/metabolism
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 100
    Publication Date: 2010-10-01
    Description: RANK ligand (RANKL), a TNF-related molecule, is essential for osteoclast formation, function and survival through interaction with its receptor RANK. Mammary glands of RANK- and RANKL-deficient mice develop normally during sexual maturation, but fail to form lobuloalveolar structures during pregnancy because of defective proliferation and increased apoptosis of mammary epithelium. It has been shown that RANKL is responsible for the major proliferative response of mouse mammary epithelium to progesterone during mammary lactational morphogenesis, and in mouse models, manipulated to induce activation of the RANK/RANKL pathway in the absence of strict hormonal control, inappropriate mammary proliferation is observed. However, there is no evidence so far of a functional contribution of RANKL to tumorigenesis. Here we show that RANK and RANKL are expressed within normal, pre-malignant and neoplastic mammary epithelium, and using complementary gain-of-function (mouse mammary tumour virus (MMTV)-RANK transgenic mice) and loss-of function (pharmacological inhibition of RANKL) approaches, define a direct contribution of this pathway in mammary tumorigenesis. Accelerated pre-neoplasias and increased mammary tumour formation were observed in MMTV-RANK transgenic mice after multiparity or treatment with carcinogen and hormone (progesterone). Reciprocally, selective pharmacological inhibition of RANKL attenuated mammary tumour development not only in hormone- and carcinogen-treated MMTV-RANK and wild-type mice, but also in the MMTV-neu transgenic spontaneous tumour model. The reduction in tumorigenesis upon RANKL inhibition was preceded by a reduction in pre-neoplasias as well as rapid and sustained reductions in hormone- and carcinogen-induced mammary epithelial proliferation and cyclin D1 levels. Collectively, our results indicate that RANKL inhibition is acting directly on hormone-induced mammary epithelium at early stages in tumorigenesis, and the permissive contribution of progesterone to increased mammary cancer incidence is due to RANKL-dependent proliferative changes in the mammary epithelium. The current study highlights a potential role for RANKL inhibition in the management of proliferative breast disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gonzalez-Suarez, Eva -- Jacob, Allison P -- Jones, Jon -- Miller, Robert -- Roudier-Meyer, Martine P -- Erwert, Ryan -- Pinkas, Jan -- Branstetter, Dan -- Dougall, William C -- England -- Nature. 2010 Nov 4;468(7320):103-7. doi: 10.1038/nature09495. Epub 2010 Sep 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Hematology/Oncology Research, Amgen Inc, Seattle, Washington 98119, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20881963" target="_blank"〉PubMed〈/a〉
    Keywords: 9,10-Dimethyl-1,2-benzanthracene/administration & dosage/adverse effects ; Animals ; Breast Neoplasms/metabolism/pathology ; Cell Proliferation/drug effects ; Cell Transformation, Neoplastic/*chemically induced/*drug effects/pathology ; Disease Models, Animal ; Epithelial Cells/drug effects/metabolism/pathology ; Female ; Humans ; Lung Neoplasms/secondary ; Mammary Neoplasms, Experimental/*chemically ; induced/genetics/metabolism/*pathology ; Mammary Tumor Virus, Mouse/genetics/physiology ; Medroxyprogesterone Acetate/administration & dosage/adverse effects ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Neoplasm Invasiveness ; Precancerous Conditions/pathology/prevention & control ; Progesterone/administration & dosage/adverse effects ; Progestins/administration & dosage/*adverse effects ; RANK Ligand/antagonists & inhibitors/genetics/*metabolism ; Receptor Activator of Nuclear Factor-kappa B/genetics/metabolism
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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