Humanized xenobiotic response in mice expressing nuclear receptor SXR

By W. Xie, J. Barwick, M. Downes, B. Blumberg, C. M. Simon, M. Nelson, B. Neuschwander‐Tetri, E. Brunt, P. Guzelian, R. Evans. Nature, 2000

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The orphan nuclear receptor SXR coordinately regulates drug metabolism and efflux (2001, background): “Several recent studies demonstrate that the orphan nuclear receptor, SXR (also known as PXR, PAR, PRR or NR1I2) has a central role in regulating CYP3A4 transcriptio”
Induction of phase I, II and III drug metabolism/transport by xenobiotics (2005, methodology): “Replacement of the mPXR with its human orthologue resulted in the xenobiotic response in this humanized mouse, and the response to xenobiotic stimulation resembled that in human (Anakk et aL, 2004; Staudinger et aL, 2001b; Xie et aL, 2000a, 2001).”
Nuclear pregnane x receptor and constitutive androstane receptor regulate overlapping but distinct sets of genes involved in xenobiotic detoxification. (2002, background): “For instance, PXR can regulate CYP2B genes and CAR can regulate CYP3A genes (Xie et al., 2000b; Goodwin et al., 2001; Smirlis et al., 2001; Wei et al., 2002).”
The nuclear pregnane X receptor: a key regulator of xenobiotic metabolism. (2002, background): “Experiments performed with transgenic mice have definitively established that PXR functions as a critical regulator of CYP3A expression in vivo (15, 16).”