A mouse model of conditional lipodystrophy

Proc Natl Acad Sci U S A. 2007 Oct 16;104(42):16627-32. doi: 10.1073/pnas.0707797104. Epub 2007 Oct 5.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipogenesis / genetics
  • Alleles
  • Animals
  • Disease Models, Animal*
  • Doxycycline / pharmacology
  • Fibroblasts / metabolism
  • Gene Expression
  • Insulin Resistance / genetics
  • Lipodystrophy / genetics*
  • Lipodystrophy / pathology
  • Mice
  • Mice, Transgenic*
  • PPAR gamma / genetics*
  • Promoter Regions, Genetic / drug effects
  • Sterol Regulatory Element Binding Protein 1 / genetics
  • Tetracycline / pharmacology
  • Trans-Activators / genetics


  • PPAR gamma
  • Srebf1 protein, mouse
  • Sterol Regulatory Element Binding Protein 1
  • Trans-Activators
  • Tetracycline
  • Doxycycline

Associated data

  • GEO/GSE9132