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AssigneesOregon Health & Science University, The Board of Trustees of the Leland Stanford Junior University
InventorsMarkus Grompe, Hisaya Azuma, Muhsen Al-Dhalimy, Mark A. Kay
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Described herein is a method of expanding human hepatocytes in vivo using an immunodeficient mouse which is further deficient in fumarylacetoacetate hydrolase (Fah). The method comprises transplanting human hepatocytes into the immunodeficient and Fah-deficient mice, allowing the hepatocytes to expand and collecting the expanded human hepatocytes. The method also allows serial transplantation of the human hepatocytes into secondary, tertiary, quaternary or additional mice. Also provided are mutant mice comprising homozygous deletions or point mutations in the Fah, Rag2 and Il2rg genes.
A method of expanding human hepatocytes in vivo, comprising:
A genetically modified mouse whose genome is homozygous for deletions or one or more point mutations in the Fah, Rag2 and Il2rg genes such that the deletions or point mutations result in loss of expression of functional FAH, RAG-2 and IL-2Rγproteins, wherein the mouse is immunodeficient and exhibits decreased liver function, and wherein human hepatocytes can be expanded in the mouse.
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