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Mice lacking transcription cofactor PRIC285 reveal attenuation of liver regeneration but are viable and develop normally
Author(s) -
Viswakarma Navin,
Matsumoto Kojiro,
Jia Yuzhi,
Rao M Sambasiva,
Reddy Janardan K
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.117.6
Subject(s) - nuclear receptor , peroxisome proliferator activated receptor , liver regeneration , biology , receptor , coactivator , phenotype , transcription factor , endocrinology , medicine , western blot , peroxisome proliferator activated receptor alpha , peroxisome , regeneration (biology) , microbiology and biotechnology , gene , biochemistry
PRIC285 was identified as a nuclear receptor transcription coactivator. To assess the biological significance of PRIC285, we developed whole‐body knock out mice using two‐ loxP and two‐ frt system and characterized them for peroxisome proliferator‐activated receptor α(PPARα)‐mediated transcriptional activation. Homozygous PRIC285 null (PRIC285 −/− ) mice appeared to develop normally and showed no consistent phenotypic differences from their wild‐type floxed littermates (PRIC285 fl/fl ). Treatment with PPARα ligands, such as Wy‐14,643 or ciprofibrate, resulted in the development of classical pleiotropic response, which includes hepatomegaly, peroxisome proliferation in hepatocytes, and increased levels of PPARα target genes. Although the PRIC285 −/− phenotype does not result in gross abnormalities in the mouse, our data suggest that it may play an important role in liver regeneration after partial hepatectomy as assessed by BrdU labeling. Western blot analysis revealed reduction of several cell cycle associated proteins in PRIC285 −/− mouse liver after partial hepatectomy as compared to wild type controls. These data indicates that although PRIC285 is not essential for PPARα‐mediated transcriptional activation in vivo it appears to affect hepatocellular proliferation. (This work was supported by NIH Grant DK083163).