Animal Models of Xenobiotic Nuclear Receptors and Their Utility in Drug Development

ANIMAL MODELS OF XENOBIOTIC NUCLEAR RECEPTORS AND THEIR UTILITY IN DRUG DEVELOPMENT 

Center for Pharmacogenetics, Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA, USA 

The establishment of NRs pregnane X receptor (PXR) and constitutive androstane receptor (CAR) as xenobiotic receptors was published in 1998 [1,2], PXR and CAR were initially found to regulate the phase ICYP3 A and CYP2B enzymes. Subsequent studies have shown that both receptors can also regulate the expression of phase II conjugating enzymes and phase III drug transporters and for this reason, PXR and CAR have been proposed to function as master xenobiotic receptors. 

Nuclear Receptors in Drug Metabolism Edited by Wen Xie Copyright 2009 John Wiley Sons, Inc. 

1 summarizes strategies to create the loss-of-function knock-out model, gain-of-function transgenic models, and the combined humanized function models [3, 6, 7], 

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