Studying HBV Infection and Therapy in Immune-Deficient NOD-Rag1-/-IL2RgammaC-null (NRG) Fumarylacetoacetate Hydrolase (Fah) Knockout Mice Transplanted with Human Hepatocytes

Methods Mol Biol. 2017;1540:267-276. doi: 10.1007/978-1-4939-6700-1_23.

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.

Keywords: Chimeric liver; HBV; Humanized mouse model; NRG/F mouse; NTBC.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • DNA, Viral
  • Disease Models, Animal
  • Genotype
  • Genotyping Techniques
  • Hepatitis B / genetics*
  • Hepatitis B / therapy
  • Hepatitis B / virology*
  • Hepatitis B virus / physiology*
  • Hepatocytes / transplantation*
  • Homeodomain Proteins / genetics*
  • Humans
  • Hydrolases / deficiency*
  • Interleukin Receptor Common gamma Subunit / deficiency*
  • Mice
  • Mice, Inbred NOD
  • Mice, Knockout
  • Transplantation, Heterologous

Substances

  • DNA, Viral
  • Homeodomain Proteins
  • IL2RG protein, human
  • Interleukin Receptor Common gamma Subunit
  • RAG-1 protein
  • Hydrolases
  • fumarylacetoacetase