Fumarylacetoacetate hydrolase (fah)-deficient and immunodeficient rats and uses thereof
AssigneeYecuris Corporation
InventorsJohn R. Bial, Elizabeth M. Wilson, Aron M. Geurts
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Abstract
Described herein are rats with a hepatic deficiency comprising decreased function, activity, or expression of an enzyme in the tyrosine catabolic pathway (such as fumarylacetoacetate hydrolase), and methods of using the same for in vivo engraftment and expansion of heterologous hepatocytes, such as human hepatocytes, analysis of human liver disease, and analysis of xenobiotics. Also disclosed is the use of immunodeficient rats for the engraftment and expansion of heterologous hepatocytes.
Claims31
A genetically modified Fah-deficient rat whose genome is homozygous for a disruption in the Fah gene such that the disruption results in loss of expression of functional FAH protein and decreased liver function.
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The method of claim 3132, further comprising expanding the collected heterologous hepatocytes by serial transplantation, wherein said serial transplantation comprises:
- collecting expanded heterologous hepatocytes from the first rat;
- transplanting the collected expanded heterologous hepatocytes from the first rat into a second rat, said second rat being a second Fah-deficient rat according to claim 1, or a second immunodeficient rat;
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- allowing the heterologous hepatocytes to expand, thereby expanding heterologous hepatocytes in vivo.
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An immunodeficient rat having a liver comprising transplanted and expanded human hepatocytes.
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Dependencies are inferred from the claim text.