A mouse model of conditional lipodystrophy

Suyeon, Kim, Huang, Li-Wen, Snow, Kathy J., Ablamunits, Vitaly, Hasham, Muneer G., H. Young, Timothy, C. Paulk, Angelique, Richardson, Joel E., Affourtit, Jason P., Shalom-Barak, Tali, J. Bult, Carol and Barak, Yaacov (2007) A mouse model of conditional lipodystrophy. Proceedings of the National Academy of Sciences, 104 42: 16627-16632. doi:10.1073/pnas.0707797104

Author Suyeon, Kim
Huang, Li-Wen
Snow, Kathy J.
Ablamunits, Vitaly
Hasham, Muneer G.
H. Young, Timothy
C. Paulk, Angelique
Richardson, Joel E.
Affourtit, Jason P.
Shalom-Barak, Tali
J. Bult, Carol
Barak, Yaacov
Title A mouse model of conditional lipodystrophy
Journal name Proceedings of the National Academy of Sciences   Check publisher's open access policy
ISSN 0027-8424
Publication date 2007-10-16
Year available 2007
Sub-type Article (original research)
DOI 10.1073/pnas.0707797104
Open Access Status Not Open Access
Volume 104
Issue 42
Start page 16627
End page 16632
Total pages 6
Place of publication United States of America
Publisher National Academy of Sciences
Language eng
Subject 11 Medical and Health Sciences
1109 Neurosciences
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 Ppargldi, a targeted allele that confers conditional dominant lipodystrophy in mice. The Ppargldi 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-PPARγ1 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.
Keyword Doxycycline
Insulin resistance
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
Queensland Brain Institute Publications
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 17 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 17 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Mon, 21 Dec 2009, 09:26:06 EST by Macushla Boyle on behalf of Queensland Brain Institute