title: Studying HBV Infection and Therapy in Immune-Deficient NOD-Rag1-/-IL2RgammaC-null (NRG) Fumarylacetoacetate Hydrolase (Fah) Knockout Mice Transplanted with Human Hepatocytes.
abstract: Chimeric mouse models with a humanized liver provide a unique tool to study hepatic virus diseases, including viral infection, viral pathogenesis, and antiviral therapy. Here we describe a detailed protocol for studying hepatitis B infection in NRG-derived fumarylacetoacetate hydrolase (Fah) knockout mice repopulated with human hepatocytes. The procedures include (1) maintenance and genotyping of the homozygous NRG-fah/fah mutant mice (NRG/F), (2) intrasplenic injection of human hepatocytes, (3) NTBC drug reduction cycling to improve human hepatocyte repopulation, (4) human albumin detection, and (5) HBV infection and detection. The method is simple and allows for highly reproducible generation of NRG/F-hu Hep mice for studying HBV infection and therapy.
authors.affiliation: Lineberger Comprehensive Cancer Center, Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.affiliation: Lineberger Comprehensive Cancer Center, Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
authors.forename: Kouki
authors.initials: K
authors.lastname: Nio
authors.affiliation: Lineberger Comprehensive Cancer Center, Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Yasui
authors.affiliation: Lineberger Comprehensive Cancer Center, Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Murphy
authors.affiliation: Lineberger Comprehensive Cancer Center, Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA. lsu@med.unc.edu.
authors.forename: Lishan
authors.initials: L
authors.lastname: Su
mesh_terms: D000818:Animals; D004279:DNA, Viral; D004195:Disease Models, Animal; D005838:Genotype; D060005:Genotyping Techniques; D006509:Hepatitis B / Q000235:genetics* / Q000628:therapy / Q000821:virology*; D006515:Hepatitis B virus / Q000502:physiology*; D022781:Hepatocytes / Q000637:transplantation*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D006867:Hydrolases / Q000172:deficiency*; D053631:Interleukin Receptor Common gamma Subunit / Q000172:deficiency*; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D014183:Transplantation, Heterologous
chemical_list: D004279:DNA, Viral; D018398:Homeodomain Proteins; C507941:IL2RG protein, human; D053631:Interleukin Receptor Common gamma Subunit; C064658:RAG-1 protein; D006867:Hydrolases; C020156:fumarylacetoacetase
keywords: Chimeric liver; HBV; Humanized mouse model; NRG/F mouse; NTBC