A mouse model of conditional lipodystrophy.
Alleles, Animals, Disease-Models-Animal, Doxycycline, Fibroblasts, Gene-Expression, Insulin-Resistance, Lipodystrophy, Mice-Transgenic, PPAR-gamma, Promoter-Regions-(Genetics), Sterol-Regulatory-Element-Binding-Protein-1, Tetracycline, Trans-Activators
Proc Natl Acad Sci U S A 2007 Oct; 104(42):16627-32.
Lipodystrophies are syndromes of adipose tissue degeneration associated with severe defects in lipid and glucose homeostasis. We report here the generation and analysis of Pparg(ldi), a targeted allele that confers conditional dominant lipodystrophy in mice. The Pparg(ldi) allele was generated by insertion of the Tet activator (tTA) and a tTA-regulated Flag-Pparg1 transgene into the Pparg gene. Unexpectedly, tTA elicits mild lipodystrophy, insulin resistance, and dyslipidemia, and the Flag-PPARgamma1 transgene surprisingly exacerbates these traits. Doxycycline can both completely prevent and reverse these phenotypes, providing a mouse model of inducible lipodystrophy. Embryonic fibroblasts from either Pparg(ldi/+) or the phenotypically similar aP2-nSrebp1c (Sr) transgenic mice undergo robust adipogenesis, suggesting that neither strain develops lipodystrophy because of defective adipocyte differentiation. In addition, Pparg(ldi/+) adipose tissue shares extensive gene expression aberrations with that of Sr mice, authenticating the phenotype at the molecular level and revealing a common expression signature of lipodystrophic fat. Thus, the Pparg(ldi/+) mouse provides a conditional animal model for studying lipodystrophy and its associated physiology and gene expression.
Kim, S; Huang, L W.; Snow, K J.; Ablamunits, V; Hasham, M G.; Young, T H.; Paulk, A C.; Richardson, J E.; Affourtit, J P.; Shalom, Barak T.; Bult, C J.; and Barak, Y, "A mouse model of conditional lipodystrophy." (2007). Faculty Research 2000 - 2009. 1583.