Recombinant non-human mammalian model for hepatitis infection and immunopathogenesis

A method of making a non-human transgenic mammal comprising an immune system, said immune system comprising:

• human T cells, human B cells, human natural killer cells, human monocytes and macrophages and human dendritic cells, so that said mammal expresses a human immune system phenotype;
• and a liver comprising human hepatocytes, so that said mammal expresses a human liver phenotype;
• said method comprising the steps of:
• (a) providing a BalbC/Rag2−/−γc−/− double knockout transgenic mammal;
• (b) transplanting human CD34+ hematopoietic stem cells into said double knockout transgenic mammal, wherein said stem cells differentiate into human T cells, human B cells, human natural killer cells, human monocytes and macrophages and human dendritic cells in said transgenic mammal;
• and
• (c) transplanting human liver cells into said double knockout transgenic mammal, wherein said liver cells form human hepatocytes in said liver of said transgenic mammal.