Generation of a humanized mouse model with both human immune system and liver cells to model hepatitis C virus infection and liver immunopathogenesis.
Establishing a small animal model that accurately recapitulates hepatotropic pathogens, including hepatitis C virus (HCV) infection and immunopathogenesis, is essential for the study of hepatitis virus-induced liver disease and for therapeutics development. This protocol describes our recently developed humanized mouse model for studying HCV and other hepatotropic infections, human immune response and hepatitis and liver fibrosis. The first 5-h stage is the isolation of human liver progenitor and hematopoietic stem cells from fetal liver. Next, AFC8 immunodeficient mice are transplanted with the isolated progenitor/stem cells. This generally takes 2 h. The transplanted mice are then treated for a month with the mouse liver apoptosis-inducing AFC8 dimerizer and left for an additional 2-month period to permit human liver and immune cell growth as well as system reconstitution and development before inoculation with HCV clinical isolates. HCV infection, human immune response and liver disease are observed with high incidence from approximately 2 months after inoculation.
Lineberger Comprehensive Cancer Center, University of North Carolina (UNC) at Chapel Hill, Chapel Hill, North Carolina, USA. moses_bility@med.unc.edu
Moses T
MT
Bility
Liguo
L
Zhang
Michael L
ML
Washburn
T Anthony
TA
Curtis
Grigoriy I
GI
Kovalev
Lishan
L
Su
D000818:Animals; D002678:Chimera / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000235:genetics; D019281:Dimerization; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006526:Hepatitis C / Q000276:immunology*; D006801:Humans; D008099:Liver / Q000276:immunology / Q000503:physiopathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D023421:Models, Animal; D016559:Tacrolimus / Q000031:analogs & derivatives
C463061:AP20187; D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse; D016559:Tacrolimus