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  • 1
    Electronic Resource
    Electronic Resource
    Chichester [u.a.] : Wiley-Blackwell
    Developmental Genetics 8 (1987), S. 249-265 
    ISSN: 0192-253X
    Keywords: trisomy ; trisomy 16 mouse ; trisomy 19 mouse ; Down syndrome ; gene dosage effects ; Life and Medical Sciences ; Genetics
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
    Notes: Autosomal aneuploidy in mammals adversely affects developmental processes. In human beings, for example, trisomy 21 is the most frequent aneuploidy detected among newborns and the most common known genetic cause of mental retardation. In this review, several hypotheses are discussed that have been proposed to explain the mechanisms by which aneuploidy (especially trisomy) disrupts development. These mechanisms included specific gene dosage effects, generalized disruption of genetic homeostasis, and the influence of the parental origin of the duplicated chromosome. The availability of specific chromosomal rearrangements in mice, coupled with selective breeding schemes, permits generation of aneuploidy of specific chromosomes or chromosomal segments on controlled genetic backgrounds, thus enabling the systematic study of the causes and consequences of defined aneuploidy. Phenotypic characteristics associated with a number of specific aneuploidies in the mouse are discussed. Emphasis is placed on the effects of trisomy 16. Genetic homology between mouse chromosome 16 and human chromosome 21 has led investigators to suggest that analogous mechanisms will be responsible for the developmental abnormalities produced in these respective aneuploidies. Analysis of trisomy 16 mice from the organismal to the subcellular level has revealed a number of phenotypic characteristics (particularly neurobiologic ones) shared with human trisomy 21. The dosage effects of shared genes (or their products) may contribute to the development of these features.
    Additional Material: 1 Ill.
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  • 2
    ISSN: 0192-253X
    Keywords: mental retardation ; Down syndrome ; cholinergic neurons ; Life and Medical Sciences ; Genetics
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
    Notes: In this study, we examined the neurochemical profiles of selected brain regions (cerebral hemispheres, diencephalon/brainstem) in fetal (day 14 to 18 gestation) trisomy 19 (Ts19) mice. The neurochemical characteristics we observed in Ts19 mice were quite different from those we observed previously in Ts16 mice. Choline acetyltransferase (ChAT) activity was reduced significantly in the cerebral hemispheres, but not in the brainstem/diencephalon, of the fetal Ts19 mouse brain, suggesting a selective vulnerability of telencephalic cholinergic neurons. Additionally, the activity of glutamic acid decarboxylase (GAD) was reduced significantly in both hemispheres and diencephalon/brainstem of late gestation Ts19 fetuses, suggesting a selective vulnerability of GABAergic neurons as well. While the levels of catecholaminergic and dopaminergic markers were reduced significantly at late gestational ages, the relative rate of turnover of dopamine (DA), measured by the ratio of DOPAC/DA, was elevated significantly in Ts19 mice. Neither reduction in the thickness of various cellular zones of the cerebral cortex nor reduced cell density of the cerebral cortex accounts for the alterations in neurochemical parameters observed in Ts19 mice. These results suggest that the effects of the triplication of specific genes on the respective chromosomes, rather than a generalized disruption of developmental homeostasis resulting from extra chromosomal material, may produce selective alterations in neurochemical and neuroanatomical markers observed in these two mouse trisomies.
    Additional Material: 5 Ill.
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  • 3
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Molecular Reproduction and Development 1 (1989), S. 233-241 
    ISSN: 1040-452X
    Keywords: Preimplantation ; Gene expression ; RNA quantity ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
    Notes: Studies of gene expression during blastocyst formation in mouse preimplantation development have been limited by the amount of RNA available per embryo. Our present approach to this problem has been to construct a large, representative, blastocyst cDNA library in λgtll. Random hexadeoxynucleotides were used as primers with total blastocyst RNA serving as template. RNA collected from 4,100 32-64 cell embryos was used to generate a library with an initial size of 30 × 106 recombinants. By using clone frequency as a measure of relative mRNA abundance, our data support previous work on the relative and absolute amounts of actin, histone H2a, and intracisternal A particle. Furthermore, we provide estimates for the abundance of cytokeratin endo A, cytokeratin endo B, and β-tubulin from clone frequency data. Insert sizes for isolated clones range from 200 bp to 3.6 kb with full-length or near-full-length insert sizes for selected clones, indicating that random primer methods generate cDNAs which can represent a significant portion of the mRNA. We have so far characterized products whose abundance is equal to or greater than 0.002% of total RNA. This library offers the potential for the analyses of presumptive regulatory gene products in the mouse preimplantation embryo which are represented as low abundance (〈1% of mRNA) RNAs.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
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