Comparative genomics of xenobiotic metabolism: a porcine-human PXR gene comparison.

摘要: The pregnane X receptor (PXR) plays a crucial role in xenobiotic and drug metabolism, being the major transcriptional regulator of cytochrome P-450 monooxygenase 3A4, which metabolizes more than 50% all clinically used drugs. Recent pharmacodynamic studies have shown that mouse is not an ideal model for predicting human clinical study outcomes. Therefore, we characterized porcine PXR (pPXR) gene to evaluate utility pig as alternate preclinical animal model. complete sequence pPXR mRNA 11 kb genomic were obtained. Similar gene, revealed multiple splice variants ligand-binding domain. All (SV) porcine-specific. mRNAs varied 3′-UTR length due differential termination specific deletions. Northern blot analyses identified high levels expression liver, small intestine, heart, kidney, colon. RT-PCR amplification detected lower tissues. Ninety-three pigs representing eight breeds analyzed single nucleotide polymorphisms (SNPs). Only one nonsynonymous SNP (S178L) was found This characterization contributes development metabolic studies.