A mouse model of conditional lipodystrophy.
Document Type
Article
Publication Date
2007
Keywords
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
First Page
16627
Last Page
16632
JAX Source
Proc Natl Acad Sci U S A 2007 Oct; 104(42):16627-32.
Abstract
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.
Recommended Citation
Kim S,
Huang LW,
Snow KJ,
Ablamunits V,
Hasham MG,
Young TH,
Paulk AC,
Richardson JE,
Affourtit JP,
Shalom BT,
Bult CJ,
Barak Y.
A mouse model of conditional lipodystrophy. Proc Natl Acad Sci U S A 2007 Oct; 104(42):16627-32.