YEARS

1996-

AUTHORS

Sarah A Comerford

TITLE

TGF/BETA1 IN CELL PROLIFERATION AND DIFFERENTIATION

ABSTRACT

The proposed research involves the characterization of transgenic mice expressing a constitutively active TGF-beta1 cDNA in liver, kidney and adipose tissue and the generation of new transgenic mice to further investigate the role of TGF-Betas in adipose and liver development and function. PEPCK-TGF-beta1 transgenic mice demonstrate a severe reduction in adipose tissue which is due to impaired adipocyte differentiation. Several human disorders such as the lipodystrophies and familial lipoprotein lipase (LPL) deficiency have been described, which result from a generalized paucity of adipose tissue and deficient LPL enzyme activity, respectively. Both of these conditions are characterized by hypertriglyceridemia, pancreatitis and hepatosplenomegaly, all of which are displayed by the PEPCK-TGF-beta1 transgenic mice. We propose to challenge PEPCK-TGF-beta1 transgenic mice to obesity-inducing regimes to assess the consequences of this severe reduction in adipose tissue on lipid metabolism. We will extend our studies into the role of TGF-betas in normal adipose development by generating transgenic mice which express a dominant-negative TGF-beta type II receptor solely in fat to attempt to block TGF-beta-mediated signaling in adipocytes. The existing PEPCK-TGFbeta1 transgenic mice will also be used to assess the role of TGF-beta1 in liver regeneration. As TGF-beta1 is postulated as being important in limiting the regenerative response, similar experiments will be carried out on transgenic animals expressing a dominant-negative TGF-beta type II receptor in liver to investigate the response in the absence of TGF-beta-mediated signaling. Finally, we will use compound hemizygous transgenic mice expressing both SV40 TAg and TGF- beta1 in liver to assess TGF-beta1's role in modulating the progression of hepatic carcinoma.

FUNDED PUBLICATIONS

  • Hepatic fibrosis, glomerulosclerosis, and a lipodystrophy-like syndrome in PEPCK-TGF-beta1 transgenic mice.
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    15 TRIPLES      14 PREDICATES      16 URIs      6 LITERALS

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    1 grants:fbb6acd047cb6f20ef8beb38ed43c919 sg:abstract The proposed research involves the characterization of transgenic mice expressing a constitutively active TGF-beta1 cDNA in liver, kidney and adipose tissue and the generation of new transgenic mice to further investigate the role of TGF-Betas in adipose and liver development and function. PEPCK-TGF-beta1 transgenic mice demonstrate a severe reduction in adipose tissue which is due to impaired adipocyte differentiation. Several human disorders such as the lipodystrophies and familial lipoprotein lipase (LPL) deficiency have been described, which result from a generalized paucity of adipose tissue and deficient LPL enzyme activity, respectively. Both of these conditions are characterized by hypertriglyceridemia, pancreatitis and hepatosplenomegaly, all of which are displayed by the PEPCK-TGF-beta1 transgenic mice. We propose to challenge PEPCK-TGF-beta1 transgenic mice to obesity-inducing regimes to assess the consequences of this severe reduction in adipose tissue on lipid metabolism. We will extend our studies into the role of TGF-betas in normal adipose development by generating transgenic mice which express a dominant-negative TGF-beta type II receptor solely in fat to attempt to block TGF-beta-mediated signaling in adipocytes. The existing PEPCK-TGFbeta1 transgenic mice will also be used to assess the role of TGF-beta1 in liver regeneration. As TGF-beta1 is postulated as being important in limiting the regenerative response, similar experiments will be carried out on transgenic animals expressing a dominant-negative TGF-beta type II receptor in liver to investigate the response in the absence of TGF-beta-mediated signaling. Finally, we will use compound hemizygous transgenic mice expressing both SV40 TAg and TGF- beta1 in liver to assess TGF-beta1's role in modulating the progression of hepatic carcinoma.
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    10 sg:scigraphId fbb6acd047cb6f20ef8beb38ed43c919
    11 sg:startYear 1996
    12 sg:title TGF/BETA1 IN CELL PROLIFERATION AND DIFFERENTIATION
    13 sg:webpage http://projectreporter.nih.gov/project_info_description.cfm?aid=2015797
    14 rdf:type sg:Grant
    15 rdfs:label Grant: TGF/BETA1 IN CELL PROLIFERATION AND DIFFERENTIATION
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