Co-chaperone CCRP/DNAJC7-regulated gene regulation in the mouse liver

Co-chaperone protein CAR Cytoplasmic Retention Protein (CCRP) interacts with various nuclear receptors and determines their localization. However, there is limited information about in vivo role of CCRP especially in nuclear receptor-mediated gene regulation. We have generated CCRP global knockout (KO) mouse and have employed whole genome microarray analysis to reveal the role of CCRP in gene regulation in the mouse liver treated with phenobarbital (CAR activator) or non-treated. Male WT and KO mice were fasted for 24 h followed by the treatment with phenobarbital or vehicle PBS for 6h. Phenobarbital significantly induced or repressed 1302 and 2744 genes in WT and KO, respectively. Interestingly, cholesterol synthesizing genes were significantly up-regulated in KO even without treatment. Mice were fasted for 24 h followed by the intraperitoneally treatment with PBS or phenobarbital at dose of 100 mg/kg body weight for 6 h, or non-treatment.