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  • American Association for the Advancement of Science (AAAS)  (5)
  • 2005-2009  (1)
  • 1985-1989  (4)
  • 1
    Publication Date: 1989-09-15
    Description: Gene targeting via homologous recombination-mediated disruption in murine embryonic stem (ES) cells has been described for a number of different genes expressed in these cells; it has not been reported for any nonexpressed genes. Pluripotent stem cell lines were isolated with homologously recombined insertions at three different loci: c-fos, which is expressed at a low level in ES cells, and two genes, adipsin and adipocyte P2 (aP2), which are transcribed specifically in adipose cells and are not expressed at detectable levels in ES cells. The frequencies at which homologous recombination events occurred did not correlate with levels of expression of the targeted genes, but did occur at rates comparable to those previously reported for genes that are actively expressed in ES cells. Injection of successfully targeted cells into mouse blastocysts resulted in the formation of chimeric mice. These studies demonstrate the feasibility of altering genes in ES cells that are expressed in a tissue-specific manner in the mouse, in order to study their function at later developmental stages.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Johnson, R S -- Sheng, M -- Greenberg, M E -- Kolodner, R D -- Papaioannou, V E -- Spiegelman, B M -- DK 31405/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1989 Sep 15;245(4923):1234-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Dana-Farber Cancer Institute, Boston, MA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2506639" target="_blank"〉PubMed〈/a〉
    Keywords: Adipose Tissue/cytology ; Animals ; Blotting, Northern ; Blotting, Southern ; Carrier Proteins/biosynthesis/*genetics ; Cell Line ; Chimera ; Complement Factor D ; DNA, Recombinant ; DNA-Binding Proteins/biosynthesis/genetics ; Fatty Acid-Binding Proteins ; Fatty Acids/metabolism ; *Gene Expression Regulation ; Genetic Vectors ; Mice ; *Neoplasm Proteins ; *Nerve Tissue Proteins ; Proto-Oncogene Proteins/biosynthesis/*genetics ; Proto-Oncogene Proteins c-fos ; RNA, Messenger/biosynthesis/genetics ; *Recombination, Genetic ; Serine Endopeptidases/*genetics ; Stem Cells/*metabolism ; Transfection
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 1989-06-23
    Description: Adipsin is a serine protease that is secreted by adipocytes into the bloodstream; it is deficient in several animal models of obesity, representing a striking example of defective gene expression in this disorder. Recombinant mouse adipsin was purified and its biochemical and enzymatic properties were studied in order to elucidate the function of this protein. Activated adipsin has little or no proteolytic activity toward most substrates but has the same activity as human complement factor D, cleaving complement factor B when it is complexed with activated complement component C3. Like authentic factor D, adipsin can activate the alternative pathway of complement, resulting in red blood cell lysis. Decreased (58 to 80 percent) complement factor D activity, relative to lean controls, was observed as a common feature of several experimental models of obesity, including the ob/ob, db/db, and monosodium glutamate (MSG)-injected mouse and the fa/fa rat. These results suggest that adipsin and the alternative pathway of complement may play an unexpected but important role in the regulation of systemic energy balance in vivo.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rosen, B S -- Cook, K S -- Yaglom, J -- Groves, D L -- Volanakis, J E -- Damm, D -- White, T -- Spiegelman, B M -- DK31403/DK/NIDDK NIH HHS/ -- DK34605/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1989 Jun 23;244(4911):1483-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Dana-Farber Cancer Institute, Boston, MA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2734615" target="_blank"〉PubMed〈/a〉
    Keywords: Adipose Tissue/metabolism ; Amino Acid Sequence ; Animals ; Cell Line ; Complement Activating Enzymes/*metabolism ; Complement Factor D/*metabolism ; Complement Pathway, Alternative ; Cricetinae ; DNA/genetics ; Gene Expression Regulation ; Humans ; Immunoblotting ; Mice ; Molecular Sequence Data ; Obesity/genetics/*immunology/metabolism ; RNA, Messenger/metabolism ; Recombinant Proteins ; Serine Endopeptidases/genetics/isolation & purification/*metabolism ; Substrate Specificity ; Transfection
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2005-08-16
    Description: Mesenchymal stem cells (MSCs) are a pluripotent cell type that can differentiate into several distinct lineages. Two key transcription factors, Runx2 and peroxisome proliferator-activated receptor gamma (PPARgamma), drive MSCs to differentiate into either osteoblasts or adipocytes, respectively. How these two transcription factors are regulated in order to specify these alternate cell fates remains a pivotal question. Here we report that a 14-3-3-binding protein, TAZ (transcriptional coactivator with PDZ-binding motif), coactivates Runx2-dependent gene transcription while repressing PPARgamma-dependent gene transcription. By modulating TAZ expression in model cell lines, mouse embryonic fibroblasts, and primary MSCs in culture and in zebrafish in vivo, we observed alterations in osteogenic versus adipogenic potential. These results indicate that TAZ functions as a molecular rheostat that modulates MSC differentiation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hong, Jeong-Ho -- Hwang, Eun Sook -- McManus, Michael T -- Amsterdam, Adam -- Tian, Yu -- Kalmukova, Ralitsa -- Mueller, Elisabetta -- Benjamin, Thomas -- Spiegelman, Bruce M -- Sharp, Phillip A -- Hopkins, Nancy -- Yaffe, Michael B -- CA042063/CA/NCI NIH HHS/ -- GM60594/GM/NIGMS NIH HHS/ -- GM68762/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2005 Aug 12;309(5737):1074-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, E18-580, Cambridge, MA 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16099986" target="_blank"〉PubMed〈/a〉
    Keywords: Adipocytes/*cytology ; Animals ; Bone Morphogenetic Protein 2 ; Bone Morphogenetic Proteins/pharmacology ; Cell Differentiation ; Cell Line ; Core Binding Factor Alpha 1 Subunit ; Gene Expression Regulation, Developmental ; Humans ; Mesenchymal Stromal Cells/*cytology/physiology ; Mice ; Neoplasm Proteins/metabolism ; Oligonucleotides, Antisense ; Osteoblasts/*cytology ; Osteocalcin/genetics ; Osteogenesis ; PPAR gamma/metabolism ; Promoter Regions, Genetic ; Protein Structure, Tertiary ; Proteins/chemistry/genetics/*physiology ; RNA, Small Interfering ; Transcription Factors/chemistry/genetics/metabolism/*physiology ; Transcriptional Activation ; Transfection ; Transforming Growth Factor beta/pharmacology ; Zebrafish ; Zebrafish Proteins/genetics/physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 1987-07-24
    Description: Adipsin, a serine protease homolog, is synthesized and secreted by adipose cells and is found in the bloodstream. The expression of adipsin messenger RNA (mRNA) and protein was analyzed in rodents during metabolic perturbations and in several experimental models of obesity. Adipsin mRNA abundance is increased in adipose tissue during fasting in normal rats and in diabetes due to streptozotocin-induced insulin deficiency. Adipsin mRNA abundance decreased during the continuous infusion of glucose, which induces a hyperglycemic, hyperinsulinemic state that is accompanied by an increased adipose mass; it is suppressed (greater than 100-fold) in two strains of genetically obese mice (db/db and ob/ob), compared to their congenic counterparts, and is also reduced when obesity is induced chemically by injection of monosodium glutamate into newborn mice. Circulating adipsin protein is decreased in these animal models of obesity, as determined by immunoblotting with antisera to adipsin. Little change in adipsin expression is observed in a model of obesity obtained by pure overfeeding of normal rats (cafeteria model). These data suggest a possible role for adipsin in the above-mentioned disordered metabolic states, and raise the possibility that adipsin expression may be used to distinguish obesities that arise from certain genetic or metabolic defects from those that result from pure overfeeding.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Flier, J S -- Cook, K S -- Usher, P -- Spiegelman, B M -- AM28082/AM/NIADDK NIH HHS/ -- AM31405/AM/NIADDK NIH HHS/ -- DK34605/DK/NIDDK NIH HHS/ -- etc. -- New York, N.Y. -- Science. 1987 Jul 24;237(4813):405-8.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3299706" target="_blank"〉PubMed〈/a〉
    Keywords: Adipose Tissue/enzymology ; Animals ; Antigen-Antibody Complex ; Complement Factor D ; Endopeptidases/*genetics/metabolism ; Immune Sera ; Mice ; Mice, Obese ; Obesity/*enzymology/genetics ; RNA, Messenger/genetics ; Reference Values ; *Serine Endopeptidases ; *Transcription, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 1987-07-24
    Description: Adipsin is a serine protease homolog whose primary structure was predicted from the nucleotide sequence of a differentiation-dependent adipocyte messenger RNA. Immunoblots probed with antisera to synthetic peptides identify two forms of adipsin that are synthesized and secreted by 3T3 adipocytes. These proteins of 44 and 37 kilodaltons are converted to 25.5 kilodaltons by enzymatic deglycosylation. Although adipsin is principally synthesized in adipose tissue, it is also produced by sciatic nerve and is found in the bloodstream. Because of the apparent restriction of adipsin synthesis to tissues highly active in lipid metabolism, its presence in serum, and its modulation in altered metabolic states, this molecule may play a previously unrecognized role in systemic lipid metabolism or energy balance.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cook, K S -- Min, H Y -- Johnson, D -- Chaplinsky, R J -- Flier, J S -- Hunt, C R -- Spiegelman, B M -- AM07230/AM/NIADDK NIH HHS/ -- AM31405/AM/NIADDK NIH HHS/ -- DK34605/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 1987 Jul 24;237(4813):402-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/3299705" target="_blank"〉PubMed〈/a〉
    Keywords: Adipose Tissue/*enzymology ; Animals ; Cells, Cultured ; Complement Factor D ; Endopeptidases/blood/genetics/*secretion ; Male ; Mice ; Molecular Weight ; Organ Culture Techniques ; RNA, Messenger/genetics ; Sciatic Nerve/*enzymology ; *Serine Endopeptidases ; Transcription, Genetic
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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