Generation of a humanized mouse model with both human immune system and liver cells to model hepatitis C virus infection and liver immunopathogenesis

Moses T. Bility, Liguo Zhang, Michael L. Washburn, T. Anthony Curtis, Grigoriy I. Kovalev, Lishan Su

Research output: Contribution to journalArticlepeer-review

54 Citations (Scopus)

Abstract

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 virusg-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 apoptosisg-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.

Original languageEnglish
Pages (from-to)1608-1617
Number of pages10
JournalNature Protocols
Volume7
Issue number9
DOIs
Publication statusPublished - Sep 2012
Externally publishedYes

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