期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1999
卷号：96
期号：4
页码：1585-1590
DOI：10.1073/pnas.96.4.1585
语种：English
出版社：The National Academy of Sciences of the United States of America
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-regulated gene expression in liver by generating mice in which the SRC-1 gene was inactivated by gene targeting. The homozygous (SRC-1-/-) mice were viable and fertile and exhibited no detectable gross phenotypic defects. When challenged with a PPAR ligand, such as ciprofibrate or Wy-14,643, the SRC-1-/- mice displayed typical pleiotropic responses, including hepatomegaly, peroxisome proliferation in hepatocytes, and increased mRNA and protein levels of genes that are regulated by PPAR. 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-mediated transcriptional activation in vivo and suggest redundancy in nuclear receptor coactivators.
