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A mouse model of conditional lipodystrophy.

Suyeon Kim1, Li-Wen Huang, Kathy J Snow

  • 1The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA.

Proceedings of the National Academy of Sciences of the United States of America
|October 9, 2007
PubMed
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Researchers developed a novel mouse model for lipodystrophy, a condition affecting fat tissue and metabolism. This inducible model allows for precise control over lipodystrophy, insulin resistance, and dyslipidemia, aiding further study.

Area of Science:

  • Metabolic disorders
  • Genetics
  • Molecular biology

Background:

  • Lipodystrophies are characterized by adipose tissue degeneration, leading to severe metabolic dysregulation.
  • Understanding the genetic and molecular underpinnings of lipodystrophies is crucial for developing effective treatments.

Purpose of the Study:

  • To generate and analyze a novel mouse model for inducible lipodystrophy.
  • To investigate the role of the Pparg gene in lipodystrophy development and associated metabolic defects.
  • To identify common molecular signatures in lipodystrophic adipose tissue.

Main Methods:

  • Generation of a targeted allele, Pparg(ldi), involving Tet-On system and Flag-PPARgamma1 transgene insertion into the Pparg gene.
  • Administration of doxycycline to control the induction and reversal of lipodystrophic phenotypes.

Related Experiment Videos

  • Analysis of adipogenesis in embryonic fibroblasts and gene expression profiling of adipose tissue.

    • Main Results:

    • The Pparg(ldi) allele confers conditional dominant lipodystrophy, insulin resistance, and dyslipidemia in mice.
    • Doxycycline treatment effectively prevents and reverses these induced metabolic phenotypes.
    • Pparg(ldi/+) mice exhibit shared gene expression aberrations with aP2-nSrebp1c (Sr) mice, revealing a common lipodystrophic fat signature.
    • Defective adipocyte differentiation was not the cause of lipodystrophy in these models.

    Conclusions:

    • The Pparg(ldi) mouse serves as a valuable conditional model for studying inducible lipodystrophy.
    • This model facilitates research into the physiology and gene expression associated with lipodystrophy.
    • The study highlights a common molecular signature in lipodystrophic adipose tissue, offering insights into disease mechanisms.