Genetically humanized mouse models of drug metabolizing enzymes and transporters and their applications

References

• Butura A, Nilsson K, Morgan K, et al. (2009). The impact of CYP2E1 on the development of alcoholic liver disease as studied in a transgenic mouse model. J Hepatol 50:572–83
   Google Scholar
• Cai H, Nguyen N, Peterkin V, et al. (2010). A humanized UGT1 mouse model expressing the UGT1A1*28 allele for assessing drug clearance by UGT1A1-dependent glucuronidation. Drug Metab Dispos 38:879–86
   PubMed Web of Science ®Google Scholar
• Cao W, Chau B, Hunter R, et al. (2005). Only low levels of exogenous N-acetyltransferase can be achieved in transgenic mice. Pharmacogenomics J 5:255–61
   PubMed Web of Science ®Google Scholar
• Cao W, Strnatka D, McQueen CA, et al. (2010). N-acetyltransferase 2 activity and folate levels. Life Sci 86:103–6
   PubMed Web of Science ®Google Scholar
• Chen C, Meng L, Ma X, et al. (2006). Urinary metabolite profiling reveals CYP1A2-mediated metabolism of NSC686288 (aminoflavone). J Pharmacol Exp Ther 318:1330–42
   PubMed Web of Science ®Google Scholar
• Chen S, Beaton D, Nguyen N, et al. (2005). Tissue-specific, inducible, and hormonal control of the human UDP-glucuronosyltransferase-1 (UGT1) locus. J Biol Chem 280:37547–57
   PubMed Web of Science ®Google Scholar
• Cheng J, Ma X, Krausz KW, et al. (2009). Rifampicin-activated human pregnane X receptor and CYP3A4 induction enhance acetaminophen-induced toxicity. Drug Metab Dispos 37:1611–21
   PubMed Web of Science ®Google Scholar
• Cheung C, Akiyama TE, Ward JM, et al. (2004). Diminished hepatocellular proliferation in mice humanized for the nuclear receptor peroxisome proliferator-activated receptor alpha. Cancer Res 64:3849–54
   PubMed Web of Science ®Google Scholar
• Cheung C, Loy S, Li GX, et al. (2011). Rapid induction of colon carcinogenesis in CYP1A-humanized mice by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and dextran sodium sulfate. Carcinogenesis 32:233–9
   PubMed Web of Science ®Google Scholar
• Cheung C, Ma X, Krausz KW, et al. (2005a). Differential metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in mice humanized for CYP1A1 and CYP1A2. Chem Res Toxicol 18:1471–8
   PubMed Web of Science ®Google Scholar
• Cheung C, Yu AM, Chen CS, et al. (2006). Growth hormone determines sexual dimorphism of hepatic cytochrome P450 3A4 expression in transgenic mice. J Pharmacol Exp Ther 316:1328–34
   PubMed Web of Science ®Google Scholar
• Cheung C, Yu AM, Ward JM, et al. (2005b). The cyp2e1-humanized transgenic mouse: role of cyp2e1 in acetaminophen hepatotoxicity. Drug Metab Dispos 33:449–57
   PubMed Web of Science ®Google Scholar
• Corchero J, Granvil CP, Akiyama TE, et al. (2001). The CYP2D6 humanized mouse: effect of the human CYP2D6 transgene and HNF4alpha on the disposition of debrisoquine in the mouse. Mol Pharmacol 60:1260–7
   PubMed Web of Science ®Google Scholar
• Derkenne S, Curran CP, Shertzer HG, et al. (2005). Theophylline pharmacokinetics: comparison of Cyp1a1(−/−) and Cyp1a2(−/−) knockout mice, humanized hCYP1A1_1A2 knock-in mice lacking either the mouse Cyp1a1 or Cyp1a2 gene, and Cyp1(+/+) wild-type mice. Pharmacogenet Genomics 15:503–11
   PubMed Web of Science ®Google Scholar
• Devoy A, Bunton-Stasyshyn RK, Tybulewicz VL, et al. (2012). Genomically humanized mice: technologies and promises. Nat Rev Genet 13:14–20
   Web of Science ®Google Scholar
• Dragin N, Dalton TP, Miller ML, et al. (2006). For dioxin-induced birth defects, mouse or human CYP1A2 in maternal liver protects whereas mouse CYP1A1 and CYP1B1 are inconsequential. J Biol Chem 281:18591–600
   PubMed Web of Science ®Google Scholar
• Dragin N, Uno S, Wang B, et al. (2007). Generation of ‘humanized' hCYP1A1_1A2_Cyp1a1/1a2(-/-) mouse line. Biochem Biophys Res Commun 359:635–42
   PubMed Web of Science ®Google Scholar
• Felmlee MA, Lon HK, Gonzalez FJ, Yu AM. (2008). Cytochrome P450 expression and regulation in CYP3A4/CYP2D6 double transgenic humanized mice. Drug Metab Dispos 36:435–41
   PubMed Web of Science ®Google Scholar
• Frederick CB, Obach RS. (2010). Metabolites in safety testing: “MIST” for the clinical pharmacologist. Clin Pharmacol Ther 87:345–50
   PubMed Web of Science ®Google Scholar
• Fujiwara R, Nguyen N, Chen S, Tukey RH. (2010). Developmental hyperbilirubinemia and CNS toxicity in mice humanized with the UDP glucuronosyltransferase 1 (UGT1) locus. Proc Natl Acad Sci U S A 107:5024–9
   PubMed Web of Science ®Google Scholar
• Giacomini KM, Huang SM, Tweedie DJ, et al. (2010). Membrane transporters in drug development. Nat Rev Drug Discov 9:215–36
   PubMed Web of Science ®Google Scholar
• Granvil CP, Yu AM, Elizondo G, et al. (2003). Expression of the human CYP3A4 gene in the small intestine of transgenic mice: in vitro metabolism and pharmacokinetics of midazolam. Drug Metab Dispos 31:548–58
   PubMed Web of Science ®Google Scholar
• Guengerich FP. (2008). Cytochrome p450 and chemical toxicology. Chem Res Toxicol 21:70–83
   PubMed Web of Science ®Google Scholar
• Guo GL, Moffit JS, Nicol CJ, et al. (2004). Enhanced acetaminophen toxicity by activation of the pregnane X receptor. Toxicol Sci 82:374–80
   PubMed Web of Science ®Google Scholar
• Harden CL. (2002). Pregnancy effects on lamotrigine levels. Epilepsy Curr 2:183
   PubMedGoogle Scholar
• Hasegawa M, Kapelyukh Y, Tahara H, 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 80:518–28
   PubMed Web of Science ®Google Scholar
• Holmstock N, Gonzalez FJ, Baes M, et al. (2013). PXR/CYP3A4-humanized mice for studying drug–drug interactions involving intestinal P-glycoprotein. Mol Pharm 10:1056–62
   PubMed Web of Science ®Google Scholar
• Jiang Z, Dalton TP, Jin L, et al. (2005). Toward the evaluation of function in genetic variability: characterizing human SNP frequencies and establishing BAC-transgenic mice carrying the human CYP1A1_CYP1A2 locus. Hum Mutat 25:196–206
   PubMed Web of Science ®Google Scholar
• Kathirvel E, Chen P, Morgan K, et al. (2010). Oxidative stress and regulation of anti-oxidant enzymes in cytochrome P4502E1 transgenic mouse model of non-alcoholic fatty liver. J Gastroenterol Hepatol 25:1136–43
   PubMed Web of Science ®Google Scholar
• Kathirvel E, Morgan K, French SW, Morgan TR. (2009). Overexpression of liver-specific cytochrome P4502E1 impairs hepatic insulin signaling in a transgenic mouse model of nonalcoholic fatty liver disease. Eur J Gastroenterol Hepatol 21:973–83
   PubMed Web of Science ®Google Scholar
• Kazuki Y, Kobayashi K, Aueviriyavit S, et al. (2012). Trans-chromosomic mice containing a human CYP3A cluster for prediction of xenobiotic metabolism in humans. Hum Mol Genet 22:578–92
   PubMed Web of Science ®Google Scholar
• Lee SS, Buters JT, Pineau T, et al. (1996). Role of CYP2E1 in the hepatotoxicity of acetaminophen. J Biol Chem 271:12063–7
   PubMed Web of Science ®Google Scholar
• Leff MA, Epstein PN, Doll MA, et al. (1999). Prostate-specific human N-acetyltransferase 2 (NAT2) expression in the mouse. J Pharmacol Exp Ther 290:182–7
   PubMed Web of Science ®Google Scholar
• Li F, Patterson AD, Krausz KW, et al. (2012). Metabolomics reveals the metabolic map of procainamide in humans and mice. Biochem Pharmacol 83:1435–44
   PubMed Web of Science ®Google Scholar
• Li Y, Yokoi T, Kitamura R, et al. (1996). Establishment of transgenic mice carrying human fetus-specific CYP3A7. Arch Biochem Biophys 329:235–40
   PubMed Web of Science ®Google Scholar
• Lofgren S, Baldwin RM, Carleros M, et al. (2009). Regulation of human CYP2C18 and CYP2C19 in transgenic mice: influence of castration, testosterone, and growth hormone. Drug Metab Dispos 37:1505–12
   PubMed Web of Science ®Google Scholar
• Lofgren S, Baldwin RM, Hiratsuka M, et al. (2008). Generation of mice transgenic for human CYP2C18 and CYP2C19: characterization of the sexually dimorphic gene and enzyme expression. Drug Metab Dispos 36:955–62
   PubMed Web of Science ®Google Scholar
• Lu Y, Wu D, Wang X, et al. (2010). Chronic alcohol-induced liver injury and oxidant stress are decreased in cytochrome P4502E1 knockout mice and restored in humanized cytochrome P4502E1 knock-in mice. Free Radic Biol Med 49:1406–16
   PubMed Web of Science ®Google Scholar
• Ma X, Cheung C, Krausz KW, et al. (2008). A double transgenic mouse model expressing human pregnane X receptor and cytochrome P450 3A4. Drug Metab Dispos 36:2506–12
   PubMed Web of Science ®Google Scholar
• Maglich JM, Stoltz CM, Goodwin B, et al. (2002). Nuclear pregnane x receptor and constitutive androstane receptor regulate overlapping but distinct sets of genes involved in xenobiotic detoxification. Mol Pharmacol 62:638–46
   PubMed Web of Science ®Google Scholar
• Miners JO, Robson RA, Birkett DJ. (1986). Paracetamol metabolism in pregnancy. Br J Clin Pharmacol 22:359–62
   PubMed Web of Science ®Google Scholar
• Morgan K, French SW, Morgan TR. (2002). Production of a cytochrome P450 2E1 transgenic mouse and initial evaluation of alcoholic liver damage. Hepatology 36:122–34
   PubMed Web of Science ®Google Scholar
• Morimura K, Cheung C, Ward JM, et al. (2006). Differential susceptibility of mice humanized for peroxisome proliferator-activated receptor alpha to Wy-14,643-induced liver tumorigenesis. Carcinogenesis 27:1074–80
   PubMed Web of Science ®Google Scholar
• Nebeker JR, Barach P, Samore MH. (2004). Clarifying adverse drug events: a clinician's guide to terminology, documentation, and reporting. Ann Intern Med 140:795–801
   PubMed Web of Science ®Google Scholar
• Omiecinski CJ, Vanden Heuvel JP, Perdew GH, Peters JM. (2011). Xenobiotic metabolism, disposition, and regulation by receptors: from biochemical phenomenon to predictors of major toxicities. Toxicol Sci 120:S49–75
   PubMed Web of Science ®Google Scholar
• Paine MF, Hart HL, Ludington SS, et al. (2006). The human intestinal cytochrome P450 “pie". Drug Metab Dispos 34:880–6
   PubMed Web of Science ®Google Scholar
• Powley MW, Frederick CB, Sistare FD, DeGeorge JJ. (2009). Safety assessment of drug metabolites: implications of regulatory guidance and potential application of genetically engineered mouse models that express human P450s. Chem Res Toxicol 22:257–62
   PubMed Web of Science ®Google Scholar
• Robison TW, Jacobs A. (2009). Metabolites in safety testing. Bioanalysis 1:1193–200
   PubMed Web of Science ®Google Scholar
• Ross J, Plummer SM, Rode A, 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 116:452–66
   PubMed Web of Science ®Google Scholar
• Sarikaya D, Bilgen C, Kamataki T, Topcu Z. (2006). Comparative cytochrome P450 -1A1, -2A6, -2B6, -2C, -2D6, -2E1, -3A5 and -4B1 expressions in human larynx tissue analysed at mRNA level. Biopharm Drug Dispos 27:353–9
   PubMed Web of Science ®Google Scholar
• Scheer N, Balimane P, Hayward MD, et al. (2012a). Generation and characterization of a novel multidrug resistance protein 2 humanized mouse line. Drug Metab Dispos 40:2212–18
   PubMed Web of Science ®Google Scholar
• Scheer N, Kapelyukh Y, Chatham L, et al. (2012b). Generation and characterization of novel cytochrome P450 Cyp2c gene cluster knockout and CYP2C9 humanized mouse lines. Mol Pharmacol 82:1022–9
   PubMed Web of Science ®Google Scholar
• Scheer N, Kapelyukh Y, McEwan J, et al. (2012c). Modeling human cytochrome P450 2D6 metabolism and drug–drug interaction by a novel panel of knockout and humanized mouse lines. Mol Pharmacol 81:63–72
   PubMed Web of Science ®Google Scholar
• Scheer N, Ross J, Kapelyukh Y, et al. (2010). In vivo responses of the human and murine pregnane X receptor to dexamethasone in mice. Drug Metab Dispos 38:1046–53
   PubMed Web of Science ®Google Scholar
• Scheer N, Ross J, Rode A, 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 118:3228–39
   PubMed Web of Science ®Google Scholar
• Scheer N, Wolf CR. (2013). Xenobiotic receptor humanized mice and their utility. Drug Metab Rev 45:110–21
   PubMed Web of Science ®Google Scholar
• Shen HW, Wu C, Jiang XL, Yu AM. (2010). Effects of monoamine oxidase inhibitor and cytochrome P450 2D6 status on 5-methoxy-N,N-dimethyltryptamine metabolism and pharmacokinetics. Biochem Pharmacol 80:122–8
   PubMed Web of Science ®Google Scholar
• Sugamori KS, Brenneman D, Grant DM. (2011). Liver-selective expression of human arylamine N-acetyltransferase NAT2 in transgenic mice. Drug Metab Dispos 39:882–90
   PubMed Web of Science ®Google Scholar
• ter Heine R, Van Waterschoot RA, Keizer RJ, et al. (2011). An integrated pharmacokinetic model for the influence of CYP3A4 expression on the in vivo disposition of lopinavir and its modulation by ritonavir. J Pharm Sci 100:2508–15
   PubMed Web of Science ®Google Scholar
• van de Steeg E, Stranecky V, Hartmannova H, et al. (2012). Complete OATP1B1 and OATP1B3 deficiency causes human Rotor syndrome by interrupting conjugated bilirubin reuptake into the liver. J Clin Invest 122:519–28
   PubMed Web of Science ®Google Scholar
• van de Steeg E, van der Kruijssen CM, Wagenaar E, et al. (2009). Methotrexate pharmacokinetics in transgenic mice with liver-specific expression of human organic anion-transporting polypeptide 1B1 (SLCO1B1). Drug Metab Dispos 37:277–81
   PubMed Web of Science ®Google Scholar
• van de Steeg E, van Esch A, Wagenaar E, et al. (2013). Influence of human OATP1B1, OATP1B3, and OATP1A2 on the pharmacokinetics of methotrexate and paclitaxel in humanized transgenic mice. Clin Cancer Res 19:821–32
   PubMed Web of Science ®Google Scholar
• van de Steeg E, Wagenaar E, van der Kruijssen CM, et al. (2010). Organic anion transporting polypeptide 1a/1b-knockout mice provide insights into hepatic handling of bilirubin, bile acids, and drugs. J Clin Invest 120:2942–52
   PubMed Web of Science ®Google Scholar
• van Herwaarden AE, Smit JW, Sparidans RW, et al. (2005). Midazolam and cyclosporin a metabolism in transgenic mice with liver-specific expression of human CYP3A4. Drug Metab Dispos 33:892–5
   PubMed Web of Science ®Google Scholar
• van Herwaarden AE, Wagenaar E, van der Kruijssen CM, et al. (2007). Knockout of cytochrome P450 3A yields new mouse models for understanding xenobiotic metabolism. J Clin Invest 117:3583–92
   PubMed Web of Science ®Google Scholar
• van Waterschoot RA, Rooswinkel RW, Sparidans RW, et al. (2009a). Inhibition and stimulation of intestinal and hepatic CYP3A activity: studies in humanized CYP3A4 transgenic mice using triazolam. Drug Metab Dispos 37:2305–13
   PubMed Web of Science ®Google Scholar
• van Waterschoot RA, Rooswinkel RW, Wagenaar E, et al. (2009b). Intestinal cytochrome P450 3A plays an important role in the regulation of detoxifying systems in the liver. FASEB J 23:224–31
   PubMed Web of Science ®Google Scholar
• van Waterschoot RA, van Herwaarden AE, Lagas JS, et al. (2008). Midazolam metabolism in cytochrome P450 3A knockout mice can be attributed to up-regulated CYP2C enzymes. Mol Pharmacol 73:1029–36
   PubMed Web of Science ®Google Scholar
• Vlaming ML, Mohrmann K, Wagenaar E, et al. (2006). Carcinogen and anticancer drug transport by Mrp2 in vivo: studies using Mrp2 (Abcc2) knockout mice. J Pharmacol Exp Ther 318:319–27
   PubMed Web of Science ®Google Scholar
• Wei Y, Wu H, Li L, et al. (2012). Generation and characterization of a CYP2A13/2B6/2F1-transgenic mouse model. Drug Metab Dispos 40:1144–50
   PubMed Web of Science ®Google Scholar
• Williams JA, Hyland R, Jones BC, et al. (2004). Drug–drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos 32:1201–8
   PubMed Web of Science ®Google Scholar
• Yang Q, Nagano T, Shah Y, et al. (2008). The PPAR alpha-humanized mouse: a model to investigate species differences in liver toxicity mediated by PPAR alpha. Toxicol Sci 101:132–9
   PubMed Web of Science ®Google Scholar
• Yu AM, Fukamachi K, Krausz KW, et al. (2005). Potential role for human cytochrome P450 3A4 in estradiol homeostasis. Endocrinology 146:2911–19
   PubMed Web of Science ®Google Scholar
• Yueh MF, Mellon PL, Tukey RH. (2011). Inhibition of human UGT2B7 gene expression in transgenic mice by the constitutive androstane receptor. Mol Pharmacol 79:1053–60
   PubMed Web of Science ®Google Scholar
• Zhang QY, Gu J, Su T, et al. (2005). Generation and characterization of a transgenic mouse model with hepatic expression of human CYP2A6. Biochem Biophys Res Commun 338:318–24
   PubMed Web of Science ®Google Scholar
• Zimniak P. (1993). Dubin-Johnson and Rotor syndromes: molecular basis and pathogenesis. Semin Liver Dis 13:248–60
   PubMed Web of Science ®Google Scholar