Transcriptional profiling of liver from wild type and PXR-null mice treated with PCN

ABSTRACT: Many environmentally-relevant chemicals and drugs activate the nuclear receptor pregnane X receptor (PXR). Activation of PXR can lead to increases in liver weight in part through hepatocyte replication similar to a large number of compounds that activate other nuclear receptors such as the peroxisome proliferator-activated receptor alpha and the constitutive activated receptor (CAR). PXR controls the expression of a large battery of genes involved in xenobiotic metabolism. Identification of genes that are accurate predictors of PXR activation would be useful in high-throughput screens to assess potential toxicity and drug-drug interactions. Here, we identified PXR-dependent genes in the mouse liver after exposure to pregnenolone 16alpha-carbinonitrile (PCN), a chemical that is often used as a model PXR agonist. The animal studies were carried out at the University of Kansas Medical Center (Kansas City, KS) under federal guidelines for the use and care of laboratory animals and was approved by the KUMC Institutional Animal Care and Use Committee. Eight-week-old adult C57BL/6 mice were purchased from Jackson Laboratories (Bar Harbor, ME). Generation of the PXR-null mice was previously described (Staudinger et al., (2001), Proc Natl Acad Sci USA 98:3369M-bM-^@M-^S3374). PXR-null breeder pairs were engineered and backcrossed into the C57BL/6 background. Adult male wild-type mice and PXR-null mice were maintained on standard laboratory chow and were allowed food and water ad libitum. All mice were treated once a day i.p. with either vehicle (corn oil) or PCN at 400 mg/kg/day for 4 days. Livers were removed 24-hrs after the last dose. Portions of the livers were rapidly snap-frozen in liquid nitrogen and stored at -70M-BM-0C until analysis. Liver gene expression analysis was performed according to the Affymetrix recommended protocol using Affymetrix Mouse Genome 430 2.0 GeneChipsM-BM-.. Total RNA (5 M-NM-

ORGANISM(S): Mus musculus

SUBMITTER: J Corton 

PROVIDER: E-GEOD-55746 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress