Pregnane X receptor- and CYP3A4-humanized mouse models and their applications

Br J Pharmacol. 2011 Jun;163(3):461-8. doi: 10.1111/j.1476-5381.2010.01129.x.


Pregnane X receptor (PXR) is a pivotal nuclear receptor modulating xenobiotic metabolism primarily through its regulation of CYP3A4, the most important enzyme involved in drug metabolism in humans. Due to the marked species differences in ligand recognition by PXR, PXR-humanized (hPXR) mice, and mice expressing human PXR and CYP3A4 (Tg3A4/hPXR) were established. hPXR and Tg3A4/hPXR mice are valuable models for investigating the role of PXR in xenobiotic metabolism and toxicity, in lipid, bile acid and steroid hormone homeostasis, and in the control of inflammation.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Animals
  • Cytochrome P-450 CYP3A / genetics*
  • Cytochrome P-450 CYP3A / metabolism
  • Disease Models, Animal*
  • Drug Evaluation, Preclinical / methods*
  • Drug-Related Side Effects and Adverse Reactions
  • Humans
  • Inflammatory Bowel Diseases / drug therapy
  • Intestinal Mucosa / metabolism
  • Liver / metabolism
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Organ Specificity
  • Pharmaceutical Preparations / metabolism*
  • Pregnane X Receptor
  • Receptors, Steroid / agonists
  • Receptors, Steroid / antagonists & inhibitors
  • Receptors, Steroid / genetics*
  • Receptors, Steroid / metabolism
  • Species Specificity
  • Xenobiotics / metabolism
  • Xenobiotics / toxicity


  • Pharmaceutical Preparations
  • Pregnane X Receptor
  • Receptors, Steroid
  • Xenobiotics
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human