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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Mouse steroid receptor coactivator-1 is not essential for peroxisome proliferator-activated receptor #alpha#-regulated gene expression
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Mouse steroid receptor coactivator-1 is not essential for peroxisome proliferator-activated receptor #alpha#-regulated gene expression

机译：小鼠类固醇受体coactivator-1对过氧化物酶体增殖物激活的受体＃alpha＃调控的基因表达不是必需的

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摘要

Peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors, and it is assumed that the biological effects of these receptors depend on interactions with recently identified coactivators, including steroid receptor coactivator-1 (SRC-1) . We assessed the in vivo function of SRC-1 on the PPAR#alpha#-regulated gene expression in liver by generating mice in which the SRC-1 gene was inacti- vated by gene targeting. The homozygous [SRC-1~(-/-)] mice were viable and fertile and exhibited no detectable gross phenotypic defects. When challenged with a PPAR#alpha# ligand, such as ciprofibrate or Wy-14,643, the SRC-1~(-/-) mice dis- played typical pleiotropic responses, including hepatomegaly, peroxisome proliferation in hepatocytes, and increased mRNA and protein levels of genes that are regulated by PPAR#alpha#. These alterations were indistinguishable from those exhibited by SRC-1~(+/+) wild-type mice fed either ciprofibrate- or Wy- 14,643-containing diets. These results indicate that SRC-1 is not essential for PPAR#alpha#-mediated transcriptional activation in vivo and suggest redundancy in nuclear receptor coactivators.
机译：过氧化物酶体增殖物激活受体（PPAR）是依赖配体的转录因子，并且假定这些受体的生物学效应取决于与最近鉴定的辅助激活剂（包括类固醇受体辅助激活剂-1（SRC-1））的相互作用。我们通过产生小鼠，其中SRC-1基因被基因靶向失活，评估了SRC-1在肝脏中对PPAR＃alpha＃调控的基因表达的体内功能。 [SRC-1〜（-/-）]纯合小鼠是活的和可育的，并且没有可检测到的总表型缺陷。当受到PPAR＃alpha＃配体（如环丙贝特或Wy-14,643）攻击时，SRC-1〜（-/-）小鼠表现出典型的多效反应，包括肝肿大，肝细胞过氧化物酶体增殖以及mRNA和蛋白质水平升高由PPAR＃alpha＃调控的基因。这些变化与饲喂含环丙贝特或含Wy-14643饮食的SRC-1〜（+ / +）野生型小鼠所表现出的变化没有区别。这些结果表明，SRC-1对于体内PPAR＃α＃介导的转录激活不是必需的，并暗示了核受体共激活子的冗余性。

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