Mouse Models for Drug Discovery pp 79-101 | Cite as
Generation of Human Liver Chimeric Mice for the Study of Human Hepatotropic Pathogens
Abstract
Human liver chimeric mice have become valuable tools for the study of human hepatotropic pathogens and for the investigation of metabolism and pharmacokinetics of novel drugs. The evolution of the underlying mouse models has been rapid in the past years. The diverse fields of applications of those model systems and their technical challenges will be discussed in this chapter.
Key words
Humanized mice Human liver chimeric mice Viral hepatitis Hepatitis C virus Hepatitis B virus Hepatitis delta virus Malaria DMPKNotes
Acknowledgements
The authors thank Jenna Gaska for edits and critical discussion of the manuscript. Work in the laboratory is in part supported by grants from the National Institutes of Health (2 R01 AI079031-05A1, 1 R01 AI107301-01, 1 R56 AI106005-01, 1R21AI117213-01), a Scholar grant from the American Cancer Society (RSG-15-048-01-MPC), and the Grand Challenge Program of Princeton University. M.v.S. is a recipient of a fellowship from the German Research Foundation (Deutsche Forschungsgemeinschaft).
References
- 1.Perz JF, Armstrong GL, Farrington LA, Hutin YJ, Bell BP (2006) The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J Hepatol 45:529–538CrossRefPubMedGoogle Scholar
- 2.Seeger C, Mason WS (2000) Hepatitis B virus biology. Microbiol Mol Biol Rev 64:51–68CrossRefPubMedPubMedCentralGoogle Scholar
- 3.Nilsson SK, Childs LM, Buckee C, Marti M (2015) Targeting human transmission biology for malaria elimination. PLoS Pathog 11:e1004871CrossRefPubMedPubMedCentralGoogle Scholar
- 4.Pileri P, Uematsu Y, Campagnoli S, Galli G, Falugi F, Petracca R, Weiner AJ, Houghton M, Rosa D, Grandi G, Abrignani S (1998) Binding of hepatitis C virus to CD81. Science 282:938–941CrossRefPubMedGoogle Scholar
- 5.Scarselli E, Ansuini H, Cerino R, Roccasecca RM, Acali S, Filocamo G, Traboni C, Nicosia A, Cortese R, Vitelli A (2002) The human scavenger receptor class B type I is a novel candidate receptor for the hepatitis C virus. EMBO J 21:5017–5025CrossRefPubMedPubMedCentralGoogle Scholar
- 6.Ploss A, Evans MJ, Gaysinskaya VA, Panis M, You H, de Jong YP, Rice CM (2009) Human occludin is a hepatitis C virus entry factor required for infection of mouse cells. Nature 457:882–886CrossRefPubMedPubMedCentralGoogle Scholar
- 7.Liu S, Yang W, Shen L, Turner JR, Coyne CB, Wang T (2009) Tight junction proteins claudin-1 and occludin control hepatitis C virus entry and are downregulated during infection to prevent superinfection. J Virol 83:2011–2014CrossRefPubMedPubMedCentralGoogle Scholar
- 8.Evans MJ, von Hahn T, Tscherne DM, Syder AJ, Panis M, Wolk B, Hatziioannou T, McKeating JA, Bieniasz PD, Rice CM (2007) Claudin-1 is a hepatitis C virus co-receptor required for a late step in entry. Nature 446:801–805CrossRefPubMedGoogle Scholar
- 9.Dorner M, Horwitz JA, Robbins JB, Barry WT, Feng Q, Mu K, Jones CT, Schoggins JW, Catanese MT, Burton DR et al (2011) A genetically humanized mouse model for hepatitis C virus infection. Nature 474:208–211CrossRefPubMedPubMedCentralGoogle Scholar
- 10.Dorner M, Rice CM, Ploss A (2013) Study of hepatitis C virus entry in genetically humanized mice. Methods 59:249–257CrossRefPubMedPubMedCentralGoogle Scholar
- 11.de Jong YP, Dorner M, Mommersteeg MC, Xiao JW, Balazs AB, Robbins JB, Winer BY, Gerges S, Vega K, Labitt RN et al (2014) Broadly neutralizing antibodies abrogate established hepatitis C virus infection. Sci Transl Med 6:254ra129CrossRefPubMedPubMedCentralGoogle Scholar
- 12.Giang E, Dorner M, Prentoe JC, Dreux M, Evans MJ, Bukh J, Rice CM, Ploss A, Burton DR, Law M (2012) Human broadly neutralizing antibodies to the envelope glycoprotein complex of hepatitis C virus. Proc Natl Acad Sci U S A 109:6205–6210CrossRefPubMedPubMedCentralGoogle Scholar
- 13.Dorner M, Horwitz JA, Donovan BM, Labitt RN, Budell WC, Friling T, Vogt A, Catanese MT, Satoh T, Kawai T et al (2013) Completion of the entire hepatitis C virus life cycle in genetically humanized mice. Nature 501:237–241CrossRefPubMedPubMedCentralGoogle Scholar
- 14.Yan H, Zhong G, Xu G, He W, Jing Z, Gao Z, Huang Y, Qi Y, Peng B, Wang H et al (2012) Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus. Elife 1:e00049CrossRefPubMedPubMedCentralGoogle Scholar
- 15.Ni Y, Lempp FA, Mehrle S, Nkongolo S, Kaufman C, Falth M, Stindt J, Koniger C, Nassal M, Kubitz R et al (2014) Hepatitis B and D viruses exploit sodium taurocholate co-transporting polypeptide for species-specific entry into hepatocytes. Gastroenterology 146:1070–1083CrossRefPubMedGoogle Scholar
- 16.He W, Ren B, Mao F, Jing Z, Li Y, Liu Y, Peng B, Yan H, Qi Y, Sun Y et al (2015) Hepatitis D virus infection of mice expressing human sodium taurocholate co-transporting polypeptide. PLoS Pathog 11:e1004840CrossRefPubMedPubMedCentralGoogle Scholar
- 17.Li H, Zhuang Q, Wang Y, Zhang T, Zhao J, Zhang Y, Zhang J, Lin Y, Yuan Q, Xia N, Han J (2014) HBV life cycle is restricted in mouse hepatocytes expressing human NTCP. Cell Mol Immunol 11:175–183CrossRefPubMedPubMedCentralGoogle Scholar
- 18.Sandgren EP, Palmiter RD, Heckel JL, Daugherty CC, Brinster RL, Degen JL (1991) Complete hepatic regeneration after somatic deletion of an albumin-plasminogen activator transgene. Cell 66:245–256CrossRefPubMedGoogle Scholar
- 19.Rhim JA, Sandgren EP, Degen JL, Palmiter RD, Brinster RL (1994) Replacement of diseased mouse liver by hepatic cell transplantation. Science 263:1149–1152CrossRefPubMedGoogle Scholar
- 20.Mercer DF, Schiller DE, Elliott JF, Douglas DN, Hao C, Rinfret A, Addison WR, Fischer KP, Churchill TA, Lakey JR et al (2001) Hepatitis C virus replication in mice with chimeric human livers. Nat Med 7:927–933CrossRefPubMedGoogle Scholar
- 21.Law M, Maruyama T, Lewis J, Giang E, Tarr AW, Stamataki Z, Gastaminza P, Chisari FV, Jones IM, Fox RI et al (2008) Broadly neutralizing antibodies protect against hepatitis C virus quasispecies challenge. Nat Med 14:25–27CrossRefPubMedGoogle Scholar
- 22.Vanwolleghem T, Bukh J, Meuleman P, Desombere I, Meunier JC, Alter H, Purcell RH, Leroux-Roels G (2008) Polyclonal immunoglobulins from a chronic hepatitis C virus patient protect human liver-chimeric mice from infection with a homologous hepatitis C virus strain. Hepatology 47:1846–1855CrossRefPubMedGoogle Scholar
- 23.Lutgehetmann M, Mancke LV, Volz T, Helbig M, Allweiss L, Bornscheuer T, Pollok JM, Lohse AW, Petersen J, Urban S, Dandri M (2012) Humanized chimeric uPA mouse model for the study of hepatitis B and D virus interactions and preclinical drug evaluation. Hepatology 55:685–694CrossRefPubMedGoogle Scholar
- 24.Volz T, Allweiss L, Ben MM, Warlich M, Lohse AW, Pollok JM, Alexandrov A, Urban S, Petersen J, Lutgehetmann M, Dandri M (2013) The entry inhibitor Myrcludex-B efficiently blocks intrahepatic virus spreading in humanized mice previously infected with hepatitis B virus. J Hepatol 58:861–867CrossRefPubMedGoogle Scholar
- 25.Sacci JB Jr, Alam U, Douglas D, Lewis J, Tyrrell DL, Azad AF, Kneteman NM (2006) Plasmodium falciparum infection and exoerythrocytic development in mice with chimeric human livers. Int J Parasitol 36:353–360CrossRefPubMedGoogle Scholar
- 26.VanBuskirk KM, O’Neill MT, De La Vega P, Maier AG, Krzych U, Williams J, Dowler MG, Sacci JB Jr, Kangwanrangsan N, Tsuboi T et al (2009) Preerythrocytic, live-attenuated Plasmodium falciparum vaccine candidates by design. Proc Natl Acad Sci U S A 106:13004–13009CrossRefPubMedPubMedCentralGoogle Scholar
- 27.Suemizu H, Hasegawa M, Kawai K, Taniguchi K, Monnai M, Wakui M, Suematsu M, Ito M, Peltz G, Nakamura M (2008) Establishment of a humanized model of liver using NOD/Shi-scid IL2Rgnull mice. Biochem Biophys Res Commun 377:248–252CrossRefPubMedGoogle Scholar
- 28.Heo J, Factor VM, Uren T, Takahama Y, Lee JS, Major M, Feinstone SM, Thorgeirsson SS (2006) Hepatic precursors derived from murine embryonic stem cells contribute to regeneration of injured liver. Hepatology 44:1478–1486CrossRefPubMedGoogle Scholar
- 29.Tesfaye A, Stift J, Maric D, Cui Q, Dienes HP, Feinstone SM (2013) Chimeric mouse model for the infection of hepatitis B and C viruses. PLoS One 8:e77298CrossRefPubMedPubMedCentralGoogle Scholar
- 30.Grompe M, al-Dhalimy M, Finegold M, Ou CN, Burlingame T, Kennaway NG, Soriano P (1993) Loss of fumarylacetoacetate hydrolase is responsible for the neonatal hepatic dysfunction phenotype of lethal albino mice. Genes Dev 7:2298–2307CrossRefPubMedGoogle Scholar
- 31.Grompe M, Lindstedt S, al-Dhalimy M, Kennaway NG, Papaconstantinou J, Torres-Ramos CA, Ou CN, Finegold M (1995) Pharmacological correction of neonatal lethal hepatic dysfunction in a murine model of hereditary tyrosinaemia type I. Nat Genet 10:453–460CrossRefPubMedGoogle Scholar
- 32.Azuma H, Paulk N, Ranade A, Dorrell C, Al-Dhalimy M, Ellis E, Strom S, Kay MA, Finegold M, Grompe M (2007) Robust expansion of human hepatocytes in Fah−/−/Rag2−/−/Il2rg−/− mice. Nat Biotechnol 25:903–910CrossRefPubMedPubMedCentralGoogle Scholar
- 33.Brehm MA, Cuthbert A, Yang C, Miller DM, DiIorio P, Laning J, Burzenski L, Gott B, Foreman O, Kavirayani A et al (2010) Parameters for establishing humanized mouse models to study human immunity: analysis of human hematopoietic stem cell engraftment in three immunodeficient strains of mice bearing the IL2rgamma(null) mutation. Clin Immunol 135:84–98CrossRefPubMedPubMedCentralGoogle Scholar
- 34.Bissig KD, Le TT, Woods NB, Verma IM (2007) Repopulation of adult and neonatal mice with human hepatocytes: a chimeric animal model. Proc Natl Acad Sci U S A 104:20507–20511CrossRefPubMedPubMedCentralGoogle Scholar
- 35.Bissig KD, Wieland SF, Tran P, Isogawa M, Le TT, Chisari FV, Verma IM (2010) Human liver chimeric mice provide a model for hepatitis B and C virus infection and treatment. J Clin Invest 120:924–930CrossRefPubMedPubMedCentralGoogle Scholar
- 36.Vaughan AM, Mikolajczak SA, Wilson EM, Grompe M, Kaushansky A, Camargo N, Bial J, Ploss A, Kappe SH (2012) Complete Plasmodium falciparum liver-stage development in liver-chimeric mice. J Clin Invest 122:3618–3628CrossRefPubMedPubMedCentralGoogle Scholar
- 37.Hasegawa M, Kawai K, Mitsui T, Taniguchi K, Monnai M, Wakui M, Ito M, Suematsu M, Peltz G, Nakamura M, Suemizu H (2011) The reconstituted ‘humanized liver’ in TK-NOG mice is mature and functional. Biochem Biophys Res Commun 405:405–410CrossRefPubMedPubMedCentralGoogle Scholar
- 38.Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676CrossRefPubMedGoogle Scholar
- 39.Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872CrossRefPubMedGoogle Scholar
- 40.Carpentier A, Tesfaye A, Chu V, Nimgaonkar I, Zhang F, Lee SB, Thorgeirsson SS, Feinstone SM, Liang TJ (2014) Engrafted human stem cell-derived hepatocytes establish an infectious HCV murine model. J Clin Invest 124:4953–4964CrossRefPubMedPubMedCentralGoogle Scholar
- 41.Yu AM, Fukamachi K, Krausz KW, Cheung C, Gonzalez FJ (2005) Potential role for human cytochrome P450 3A4 in estradiol homeostasis. Endocrinology 146:2911–2919CrossRefPubMedGoogle Scholar
- 42.van Herwaarden AE, Wagenaar E, van der Kruijssen CM, van Waterschoot RA, Smit JW, Song JY, van der Valk MA, van Tellingen O, van der Hoorn JW, Rosing H et al (2007) Knockout of cytochrome P450 3A yields new mouse models for understanding xenobiotic metabolism. J Clin Invest 117:3583–3592CrossRefPubMedPubMedCentralGoogle Scholar
- 43.Katoh M, Matsui T, Nakajima M, Tateno C, Kataoka M, Soeno Y, Horie T, Iwasaki K, Yoshizato K, Yokoi T (2004) Expression of human cytochromes P450 in chimeric mice with humanized liver. Drug Metab Dispos 32:1402–1410CrossRefPubMedGoogle Scholar
- 44.Katoh M, Sawada T, Soeno Y, Nakajima M, Tateno C, Yoshizato K, Yokoi T (2007) In vivo drug metabolism model for human cytochrome P450 enzyme using chimeric mice with humanized liver. J Pharm Sci 96:428–437CrossRefPubMedGoogle Scholar
- 45.Emoto C, Yamato Y, Sato Y, Ohshita H, Katoh M, Tateno C, Yokoi T, Yoshizato K, Iwasaki K (2008) Non-invasive method to detect induction of CYP3A4 in chimeric mice with a humanized liver. Xenobiotica 38:239–248CrossRefPubMedGoogle Scholar
- 46.Katoh M, Watanabe M, Tabata T, Sato Y, Nakajima M, Nishimura M, Naito S, Tateno C, Iwasaki K, Yoshizato K, Yokoi T (2005) In vivo induction of human cytochrome P450 3A4 by rifabutin in chimeric mice with humanized liver. Xenobiotica 35:863–875CrossRefPubMedGoogle Scholar
- 47.Sanoh S, Horiguchi A, Sugihara K, Kotake Y, Tayama Y, Uramaru N, Ohshita H, Tateno C, Horie T, Kitamura S, Ohta S (2012) Predictability of metabolism of ibuprofen and naproxen using chimeric mice with human hepatocytes. Drug Metab Dispos 40:2267–2272CrossRefPubMedGoogle Scholar
- 48.Washburn ML, Bility MT, Zhang L, Kovalev GI, Buntzman A, Frelinger JA, Barry W, Ploss A, Rice CM, Su L (2011) A humanized mouse model to study hepatitis C virus infection, immune response, and liver disease. Gastroenterology 140:1334–1344CrossRefPubMedPubMedCentralGoogle Scholar
- 49.Gutti TL, Knibbe JS, Makarov E, Zhang J, Yannam GR, Gorantla S, Sun Y, Mercer DF, Suemizu H, Wisecarver JL et al (2014) Human hepatocytes and hematolymphoid dual reconstitution in treosulfan-conditioned uPA-NOG mice. Am J Pathol 184:101–109CrossRefPubMedPubMedCentralGoogle Scholar
- 50.Wilson EM, Bial J, Tarlow B, Bial G, Jensen B, Greiner DL, Brehm MA, Grompe M (2014) Extensive double humanization of both liver and hematopoiesis in FRGN mice. Stem Cell Res 13:404–412CrossRefPubMedGoogle Scholar
- 51.Kawahara T, Toso C, Douglas DN, Nourbakhsh M, Lewis JT, Tyrrell DL, Lund GA, Churchill TA, Kneteman NM (2010) Factors affecting hepatocyte isolation, engraftment, and replication in an in vivo model. Liver Transpl 16:974–982CrossRefPubMedGoogle Scholar
- 52.Vanwolleghem T, Libbrecht L, Hansen BE, Desombere I, Roskams T, Meuleman P, Leroux-Roels G (2010) Factors determining successful engraftment of hepatocytes and susceptibility to hepatitis B and C virus infection in uPA-SCID mice. J Hepatol 53:468–476CrossRefPubMedGoogle Scholar
- 53.Kelsey G, Ruppert S, Beermann F, Grund C, Tanguay RM, Schutz G (1993) Rescue of mice homozygous for lethal albino deletions: implications for an animal model for the human liver disease tyrosinemia type 1. Genes Dev 7:2285–2297CrossRefPubMedGoogle Scholar