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J. Lipid Res.
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Originally published In Press as doi:10.1194/jlr.M800531-JLR200 on March 12, 2009

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Journal of Lipid Research, Vol. 50, 1269-1280, July 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

Adult-onset degeneration of adipose tissue in mice deficient for the Sox8 transcription factor

Sabine I. E. Guth{dagger}, Katy Schmidt{dagger}, Andreas Hess* and Michael Wegner1,{dagger}

{dagger} Institut für Biochemie, Emil-Fischer-Zentrum, Universität Erlangen, Erlangen, Germany
* Institut für Pharmakologie, Emil-Fischer-Zentrum, Universität Erlangen, Erlangen, Germany

This work was supported by Grant SFB473 (M.W.) from the Deutsche Forschungsgemeinschaft.

Published, JLR Papers in Press, March 12, 2009.

1 To whom correspondence should be addressed. e-mail: m.wegner{at}biochem.uni-erlangen.de

Although the transcription factor Sox8 is broadly expressed during embryogenesis in developing ectodermal and mesodermal tissues, mice develop surprisingly normally in the absence of Sox8. Phenotypes in adult Sox8-deficient mice include mild osteopenia, late-onset male infertility, and reduced weight. We show here that progressive degeneration of adipose tissue in adult Sox8-deficient mice significantly contributes to weight reduction. Although serum levels of leptin, IGF-1, and noradrenaline were altered in Sox8-deficient mice, these changes could not explain the observed phenotype. Other serum parameters, including indicators of glucose metabolism, were largely normal. However, expression of the preadipocyte marker Pref-1 was elevated in adipose tissues of Sox8-deficient mice. This increase correlated with an impaired differentiation of Sox8-deficient fibroblasts to adipocytes in culture, a defect that could be rescued by reintroducing Sox8 into the cells. Furthermore, Sox8 levels were higher in mesodermal precursors than in mature adipocytes. We postulate a precursor-intrinsic role of Sox8 during replenishment of the adipocyte pool in adult mice and assume that disturbance of this function significantly contributes to adipose tissue degeneration in Sox8-deficient mice.

Supplementary key words high-mobility-group • mesoderm • Sry • transgenic mouse model

Abbreviations: BAT, brown adipose tissue; dpc, days post coitum; FCS, fetal calf serum; MEF, mouse embryonic fibroblasts; WAT, white adipose tissue


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