TY - JOUR
T1 - Mouse steroid receptor coactivator-1 is not essential for peroxisome proliferator-activated receptor α-regulated gene expression
AU - Qi, Chao
AU - Zhu, Yijun
AU - Pan, Jie
AU - Yeldandi, Anjana V.
AU - Rao, M. Sambasiva
AU - Maeda, Nobuyo
AU - Subbarao, V.
AU - Pulikuri, Sujata
AU - Hashimoto, Takashi
AU - Reddy, Janardan K.
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 1999/2/16
Y1 - 1999/2/16
N2 - 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 PPARα-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 PPARα 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 PPARα. 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 PPARα-mediated transcriptional activation in vivo and suggest redundancy in nuclear receptor coactivators.
AB - 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 PPARα-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 PPARα 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 PPARα. 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 PPARα-mediated transcriptional activation in vivo and suggest redundancy in nuclear receptor coactivators.
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U2 - 10.1073/pnas.96.4.1585
DO - 10.1073/pnas.96.4.1585
M3 - Article
C2 - 9990068
AN - SCOPUS:13044266369
VL - 96
SP - 1585
EP - 1590
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 4
ER -