Xenobiotic receptor humanized mice and their utility

References

• Arnold, K. A., Eichelbaum, M., Burk, O. (2004). Alternative splicing affects the function and tissue-specific expression of the human constitutive androstane receptor. Nucl Recept 2:1.
   PubMedGoogle Scholar
• Auerbach, S. S., Dekeyser, J. G., Stoner, M. A., Omiecinski, C. J. (2007). CAR2 displays unique ligand binding and RXRalpha heterodimerization characteristics. Drug Metab Dispos 35:428–439.
   PubMed Web of Science ®Google Scholar
• Auerbach, S. S., Ramsden, R., Stoner, M. A., Verlinde, C., Hassett, C., Omiecinski, C. J. (2003). Alternatively spliced isoforms of the human constitutive androstane receptor. Nucleic Acids Res 31:3194–3207.
   PubMed Web of Science ®Google Scholar
• Chen, J., Raymond, K. (2006). Roles of rifampicin in drug-drug interactions: underlying molecular mechanisms involving the nuclear pregnane X receptor. Ann Clin Microbiol Antimicrob 5:3.
   PubMedGoogle Scholar
• Cheng, J., Ma, X., Krausz, K. W., Idle, J. R., Gonzalez, F. J. (2009). Rifampicin-activated human pregnane X receptor and CYP3A4 induction enhance acetaminophen-induced toxicity. Drug Metab Dispos 37:1611–1621.
   PubMed Web of Science ®Google Scholar
• Cheng, J., Shah, Y. M., Ma, X., Pang, X., Tanaka, T., Kodama, T., et al. (2010). Therapeutic role of rifaximin in inflammatory bowel disease: clinical implication of human pregnane X receptor activation. J Pharmacol Exp Ther 335:32–41.
   PubMed Web of Science ®Google Scholar
• Cheung, C., Akiyama, T. E., Ward, J. M., Nicol, C. J., Feigenbaum L., Vinson, C., et al. (2004). Diminished hepatocellular proliferation in mice humanized for the nuclear receptor peroxisome proliferator-activated receptor alpha. Cancer Res 64:3849–3854.
   PubMed Web of Science ®Google Scholar
• Denison, M. S., Nagy, S. R. (2003). Activation of the aryl hydrocarbon receptor by structurally diverse exogenous and endogenous chemicals. Annu Rev Pharmacol Toxicol 43:309–334.
   PubMed Web of Science ®Google Scholar
• Ellinger-Ziegelbauer, H., Stuart, B., Wahle, B., Bomann, W., Ahr, H. J. (2005). Comparison of the expression profiles induced by genotoxic and nongenotoxic carcinogens in rat liver. 5575:61–84.
   Google Scholar
• Ema, M., Ohe, N., Suzuki, M., Mimura, J., Sogawa, K., Ikawa, S., et al. (1994). Dioxin binding activities of polymorphic forms of mouse and human arylhydrocarbon receptors. J Biol Chem 269:27337–27343.
   PubMed Web of Science ®Google Scholar
• Fievet, C., Fruchart, J. C., Staels, B. (2006). PPARalpha and PPARgamma dual agonists for the treatment of type 2 diabetes and the metabolic syndrome. Curr Opin Pharmacol 6:606–614.
   PubMed Web of Science ®Google Scholar
• Flaveny, C. A., Murray, I. A., Chiaro, C. R., Perdew, G. H. (2009). Ligand selectivity and gene regulation by the human aryl hydrocarbon receptor in transgenic mice. Mol Pharmacol 75:1412–1420.
   PubMed Web of Science ®Google Scholar
• Flaveny, C. A., Murray, I. A., Perdew, G. H. (2010). Differential gene regulation by the human and mouse aryl hydrocarbon receptor. Toxicol Sci 114:217–225.
   PubMed Web of Science ®Google Scholar
• Fruchart, J. C., Duriez, P., Staels, B. (1999). Peroxisome proliferator-activated receptor-alpha activators regulate genes governing lipoprotein metabolism, vascular inflammation, and atherosclerosis. Curr Opin Lipidol 10:245–257.
   PubMed Web of Science ®Google Scholar
• Fujii-Kuriyama, Y., Kawajiri, K. (2010). Molecular mechanisms of the physiological functions of the aryl hydrocarbon (dioxin) receptor, a multifunctional regulator that senses and responds to environmental stimuli. Proc Jpn Acad Ser B Phys Biol Sci 86:40–53.
   PubMed Web of Science ®Google Scholar
• Fukuen, S., Fukuda, T., Matsuda, H., Sumida, A., Yamamoto, I., Inaba, T., et al. (2002). Identification of the novel splicing variants for the hPXR in human livers. Biochem Biophys Res Commun 298:433–438.
   PubMed Web of Science ®Google Scholar
• Gao, J., He, J., Zhai, Y., Wada, T., Xie, W. (2009). The constitutive androstane receptor is an anti-obesity nuclear receptor that improves insulin sensitivity. J Biol Chem 284:25984–25992.
   PubMed Web of Science ®Google Scholar
• Gao, J., Xie, W. (2010). Pregnane X receptor and constitutive androstane receptor at the crossroads of drug metabolism and energy metabolism. Drug Metab Dispos 38:2091–2095.
   PubMed Web of Science ®Google Scholar
• Gervois, P., Torra, I. P., Chinetti, G., Grotzinger, T., Dubois, G., Fruchart, J. C., et al. (1999). A truncated human peroxisome proliferator-activated receptor alpha splice variant with dominant negative activity. Mol Endocrinol 13:1535–1549.
   PubMed Web of Science ®Google Scholar
• Gong, H., Singh, S. V., Singh, S. P., Mu, Y., Lee, J. H., Saini, S. P., et al. (2006). Orphan nuclear receptor pregnane X receptor sensitizes oxidative stress responses in transgenic mice and cancerous cells. Mol Endocrinol 20:279–290.
   PubMed Web of Science ®Google Scholar
• Gonzalez, F. J., Peters, J. M., Cattley, R. C. (1998). Mechanism of action of the nongenotoxic peroxisome proliferators: role of the peroxisome proliferator-activator receptor alpha. J Natl Cancer Inst 90:1702–1709.
   PubMed Web of Science ®Google Scholar
• Gonzalez, F. J., Shah, Y. M. (2008). PPARalpha: mechanism of species differences and hepatocarcinogenesis of peroxisome proliferators. Toxicology 246:2–8.
   PubMed Web of Science ®Google Scholar
• Hankinson, O. (1995). The aryl hydrocarbon receptor complex. Annu Rev Pharmacol Toxicol 35:307–340.
   PubMed Web of Science ®Google Scholar
• Hasegawa, M., Kapelyukh, Y., Tahara H., Seibler, J., Rode, A., Krueger, S, et al. (2011). Quantitative prediction of human pregnane X receptor and cytochrome P450 3A4 mediated drug-drug interaction in a novel multiple humanized mouse line. Mol Pharmacol 80:518–528.
   PubMed Web of Science ®Google Scholar
• Hirose, Y., Nagahori, H., Yamada, T., Deguchi, Y., Tomigahara, Y., Nishioka, K., et al. (2009). Comparison of the effects of the synthetic pyrethroid Metofluthrin and phenobarbital on CYP2B form induction and replicative DNA synthesis in cultured rat and human hepatocytes. Toxicology 258:64–69.
   PubMed Web of Science ®Google Scholar
• Huang, W., Zhang, J., Washington, M., Liu, J., Parant, J. M., Lozano, G., et al. (2005). Xenobiotic stress induces hepatomegaly and liver tumors via the nuclear receptor constitutive androstane receptor. Mol Endocrinol 19:1646–1653.
   PubMed Web of Science ®Google Scholar
• Hustert, E., Zibat, A., Presecan-Siedel, E., Eiselt, R., Mueller, R., Fuss, C., et al. (2001). Natural protein variants of pregnane X receptor with altered transactivation activity toward CYP3A4. Drug Metab Dispos 29:1454–1459.
   PubMed Web of Science ®Google Scholar
• Igarashi, K., Kitajima, S., Aisaki, K., Tanemura, K., Taquahashi, Y., Moriyama, N., et al. (2012). Development of humanized steroid and xenobiotic receptor mouse by homologous knock-in of the human steroid and xenobiotic receptor ligand binding domain sequence. J Toxicol Sci 37:373–380.
   PubMed Web of Science ®Google Scholar
• Jones, S. A., Moore, L. B., Shenk, J. L., Wisely, G. B., Hamilton, G. A., McKee, D. D., et al. (2000). The pregnane X receptor: a promiscuous xenobiotic receptor that has diverged during evolution. Mol Endocrinol 14:27–39.
   PubMed Web of Science ®Google Scholar
• Kakizaki, S., Takizawa, D., Tojima, H., Horiguchi, N., Yamazaki, Y., Mori, M. (2011). Nuclear receptors CAR and PXR: therapeutic targets for cholestatic liver disease. Front Biosci 17:2988–3005.
   Google Scholar
• Kim, S., Pray, D., Zheng, M., Morgan, D. G., Pizzano, J. G., Zoeckler, M. E., et al. (2008). Quantitative relationship between rifampicin exposure and induction of Cyp3a11 in SXR humanized mice: extrapolation to human CYP3A4 induction potential. Drug Metab Lett 2:169–175.
   PubMedGoogle Scholar
• Kliewer, S. A., Goodwin, B., Willson, T. M. (2002). The nuclear pregnane X receptor: a key regulator of xenobiotic metabolism. Endocr Rev 23:687–702.
   PubMed Web of Science ®Google Scholar
• Konno, Y., Negishi, M., Kodama, S. (2008). The roles of nuclear receptors CAR and PXR in hepatic energy metabolism. Drug Metab Pharmacokinet 23:8–13.
   PubMed Web of Science ®Google Scholar
• Kroetz, D. L., Yook, P., Costet, P., Bianchi, P., Pineau, T. (1998). Peroxisome proliferator-activated receptor alpha controls the hepatic CYP4A induction adaptive response to starvation and diabetes. J Biol Chem 273:31581–31589.
   PubMed Web of Science ®Google Scholar
• Kublbeck, J., Laitinen, T., Jyrkkarinne, J., Rousu, T., Tolonen, A., Abel, T., et al. (2011). Use of comprehensive screening methods to detect selective human CAR activators. Biochem Pharmacol 82:1994–2007.
   PubMed Web of Science ®Google Scholar
• Lake, B. G. (2009). Species differences in the hepatic effects of inducers of CYP2B and CYP4A subfamily forms: relationship to rodent liver tumour formation. Xenobiotica 39:582–596.
   PubMed Web of Science ®Google Scholar
• Lichti-Kaiser, K., Staudinger, J. L. (2008). The traditional Chinese herbal remedy tian xian activates pregnane X receptor and induces CYP3A gene expression in hepatocytes. Drug Metab Dispos 36:1538–1545.
   PubMed Web of Science ®Google Scholar
• Ma, X., Cheung, C., Krausz, K. W., Shah, Y. M., Wang, T., Idle, J. R., et al. (2008). A double transgenic mouse model expressing human pregnane X receptor and cytochrome P450 3A4. Drug Metab Dispos 36:2506–2512.
   PubMed Web of Science ®Google Scholar
• Ma, X., Shah, Y., Cheung, C., Guo, G. L., Feigenbaum, L., Krausz, K. W., et al. (2007a). The PREgnane X receptor gene-humanized mouse: a model for investigating drug-drug interactions mediated by cytochromes P450 3A. Drug Metab Dispos 35:194–200.
   PubMed Web of Science ®Google Scholar
• Ma, X., Shah, Y. M., Guo, G. L., Wang, T., Krausz, K. W., Idle, J. R., et al. (2007b). Rifaximin is a gut-specific human pregnane x receptor activator. J Pharmacol Exp Ther 322:391–398.
   PubMed Web of Science ®Google Scholar
• Maglich, J. M., Stoltz, C. M., Goodwin, B., Hawkins-Brown, D., Moore, J. T., Kliewer, S. A. (2002). Nuclear pregnane x receptor and constitutive androstane receptor regulate overlapping but distinct sets of genes involved in xenobiotic detoxification. Mol Pharmacol 62:638–646.
   PubMed Web of Science ®Google Scholar
• McMillan, B. J., Bradfield, C. A. (2007). The aryl hydrocarbon receptor sans xenobiotics: endogenous function in genetic model systems. Mol Pharmacol 72:487–498.
   PubMed Web of Science ®Google Scholar
• Moore, D. D., Kato, S., Xie, W., Mangelsdorf, D. J., Schmidt, D. R., Xiao, R., et al. (2006). International Union of Pharmacology. LXII. The NR1H and NR1I receptors: constitutive androstane receptor, pregnene X receptor, farnesoid X receptor alpha, farnesoid X receptor beta, liver X receptor alpha, liver X receptor beta, and vitamin D receptor. Pharmacol Rev 58:742–759.
   PubMed Web of Science ®Google Scholar
• Moreau, A., Vilarem, M. J., Maurel, P., Pascussi, J. M. (2008). Xenoreceptors CAR and PXR activation and consequences on lipid metabolism, glucose homeostasis, and inflammatory response. Mol Pharm 5:35–41.
   PubMed Web of Science ®Google Scholar
• Moriguchi, T., Motohashi, H., Hosoya, T., Nakajima, O., Takahashi, S., Ohsako, S., et al. (2003). Distinct response to dioxin in an arylhydrocarbon receptor (AHR)-humanized mouse. Proc Natl Acad Sci U S A 100:5652–5657.
   PubMed Web of Science ®Google Scholar
• Morimura, K., Cheung, C., Ward, J. M., Reddy, J. K., Gonzalez, F. J. (2006). Differential susceptibility of mice humanized for peroxisome proliferator-activated receptor alpha to Wy-14,643-induced liver tumorigenesis. Carcinogenesis 27:1074–1080.
   PubMed Web of Science ®Google Scholar
• Mota, L. C., Barfield, C., Hernandez, J. P., Baldwin, W. S. (2011). Nonylphenol-mediated CYP induction is PXR-dependent: The use of humanized mice and human hepatocytes suggests that hPXR is less sensitive than mouse PXR to nonylphenol treatment. Toxicol Appl Pharmacol 252:259–267.
   PubMed Web of Science ®Google Scholar
• Okey, A. B., Vella, L. M., Harper, P. A. (1989). Detection and characterization of a low affinity form of cytosolic Ah receptor in livers of mice nonresponsive to induction of cytochrome P1-450 by 3-methylcholanthrene. Mol Pharmacol 35:823–830.
   PubMed Web of Science ®Google Scholar
• Omiecinski, C. J., Vanden Heuvel, J. P., Perdew, G. H., Peters, J. M. (2011). Xenobiotic metabolism, disposition, and regulation by receptors: from biochemical phenomenon to predictors of major toxicities. Toxicol Sci 120 (Suppl 1):S49–S75.
   PubMed Web of Science ®Google Scholar
• Park, C. W., Zhang, Y., Zhang, X., Wu, J., Chen, L., Cha, D. R., et al. (2006). PPARalpha agonist fenofibrate improves diabetic nephropathy in db/db mice. Kidney Int 69:1511–1517.
   PubMed Web of Science ®Google Scholar
• Parzefall, W., Erber, E., Sedivy, R., Schulte-Hermann, R. (1991). Testing for induction of DNA synthesis in human hepatocyte primary cultures by rat liver tumor promoters. Cancer Res 51:1143–1147.
   PubMed Web of Science ®Google Scholar
• Pohjanvirta, R., Viluksela, M., Tuomisto, J. T., Unkila, M., Karasinska, J., Franc, M. A., et al. (1999). Physicochemical differences in the AH receptors of the most TCDD-susceptible and the most TCDD-resistant rat strains. Toxicol Appl Pharmacol 155:82–95.
   PubMed Web of Science ®Google Scholar
• Ramadoss, P., Perdew, G. H. (2004). Use of 2-azido-3-[125I]iodo-7,8-dibromodibenzo-p-dioxin as a probe to determine the relative ligand affinity of human versus mouse aryl hydrocarbon receptor in cultured cells. Mol Pharmacol 66:129–136.
   PubMed Web of Science ®Google Scholar
• Rencurel, F., Stenhouse, A., Hawley, S. A., Friedberg, T., Hardie, D. G., Sutherland, C., et al. (2005). AMP-activated protein kinase mediates phenobarbital induction of CYP2B gene expression in hepatocytes and a newly derived human hepatoma cell line. J Biol Chem 280:4367–4373.
   PubMed Web of Science ®Google Scholar
• Ross, J., Plummer, S. M., Rode, A., Scheer, N., Bowers, C. C., Vogel, O., et al. (2010). Human constitutive androstane receptor (CAR) and pregnane X receptor (PXR) support the hypertrophic but not the hyperplastic response to the murine non-genotoxic hepatocarcinogens phenobarbital and chlordane in vivo. Toxicol Sci 116:452–466.
   PubMed Web of Science ®Google Scholar
• Saini, S. P., Sonoda, J., Xu, L., Toma, D., Uppal, H., Mu, Y., et al. (2004). A novel constitutive androstane receptor-mediated and CYP3A-independent pathway of bile acid detoxification. Mol Pharmacol 65:292–300.
   PubMed Web of Science ®Google Scholar
• Scheer, N., Ross, J., Kapelyukh, Y., Rode, A., Wolf, C. R. (2010). In vivo responses of the human and murine pregnane X receptor to dexamethasone in mice. Drug Metab Dispos 38:1046–1053.
   PubMed Web of Science ®Google Scholar
• Scheer, N., Ross, J., Rode, A., Zevnik, B., Niehaves, S., Faust, N., et al. (2008). A novel panel of mouse models to evaluate the role of human pregnane X receptor and constitutive androstane receptor in drug response. J Clin Invest 118:3228–3239.
   PubMed Web of Science ®Google Scholar
• Shirai, H., Oishi, K., Kudo, T., Shibata, S., Ishida, N. (2007). PPARalpha is a potential therapeutic target of drugs to treat circadian rhythm sleep disorders. Biochem Biophys Res Commun 357:679–682.
   PubMed Web of Science ®Google Scholar
• Shirinsky, I. V., Shirinsky, V. S. (2011). Targeting nuclear hormone receptors: PPARalpha agonists as potential disease-modifying drugs for rheumatoid arthritis. Int J Rheumatol 2011:937843.
   PubMedGoogle Scholar
• Staudinger, J. L., Goodwin, B., Jones, S. A., Hawkins-Brown, D., MacKenzie, K. I., LaTour, A., et al. (2001). The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity. Proc Natl Acad Sci U S A 98:3369–3374.
   PubMed Web of Science ®Google Scholar
• Wada, T., Gao, J., Xie, W. (2009). PXR and CAR in energy metabolism. Trends Endocrinol Metab 20:273–279.
   PubMed Web of Science ®Google Scholar
• Wallace, K., Cowie, D. E., Konstantinou, D. K., Hill, S. J., Tjelle, T. E., Axon, A., et al. (2010). The PXR is a drug target for chronic inflammatory liver disease. J Steroid Biochem Mol Biol 120:137–148.
   PubMed Web of Science ®Google Scholar
• Woods, C. G., Heuvel, J. P., Rusyn, I. (2007). Genomic profiling in nuclear receptor-mediated toxicity. Toxicol Pathol 35:474–494.
   PubMed Web of Science ®Google Scholar
• Xie, W., Barwick, J. L., Downes, M., Blumberg, B., Simon, C. M., Nelson, M. C., et al. (2000). Humanized xenobiotic response in mice expressing nuclear receptor SXR. Nature 406:435–439.
   PubMed Web of Science ®Google Scholar
• Xie, W., Radominska-Pandya, A., Shi Y., Simon, C. M., Nelson, M. C., Ong, E. S., et al. (2001). An essential role for nuclear receptors SXR/PXR in detoxification of cholestatic bile acids. Proc Natl Acad Sci U S A 98:3375–3380.
   PubMed Web of Science ®Google Scholar
• Yamamoto, Y., Moore, R., Goldsworthy, T. L., Negishi, M., Maronpot, R. R. (2004). The orphan nuclear receptor constitutive active/androstane receptor is essential for liver tumor promotion by phenobarbital in mice. Cancer Res 64:7197–7200.
   PubMed Web of Science ®Google Scholar
• Yang, Q., Nagano, T., Shah, Y., Cheung, C., Ito, S., Gonzalez, F. J. (2008). The PPAR alpha-humanized mouse: a model to investigate species differences in liver toxicity mediated by PPAR alpha. Toxicol Sci 101:132–139.
   PubMed Web of Science ®Google Scholar
• Zhang, J., Huang, W., Chua, S. S., Wei, P., Moore, D. D. (2002). Modulation of acetaminophen-induced hepatotoxicity by the xenobiotic receptor CAR. Science 298:422–424.
   PubMed Web of Science ®Google Scholar
• Zhou, J., Zhai, Y., Mu, Y., Gong, H., Uppal, H., Toma, D., et al. (2006). A novel pregnane X receptor-mediated and sterol regulatory element-binding protein-independent lipogenic pathway. J Biol Chem 281:15013–15020.
   PubMed Web of Science ®Google Scholar