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.
Claims20
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.
A method of expanding human hepatocytes in vivo, comprising:
- transplanting heterologous hepatocytes into a first rat, wherein said first rat is:
- 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 FAR protein and decreased liver function, or
- an immunodeficient rat, wherein the immunodeficiency of the rat is due to a genetic alteration, immunosuppression, or a combination thereof, and
- allowing the heterologous hepatocytes to expand, thereby expanding heterologous hepatocytes in vivo.
An immunodeficient rat having a liver comprising transplanted and expanded human hepatocytes, wherein the immunodeficiency of the rat is due to a genetic alteration, immunosuppression, or a combination thereof.
Dependencies are inferred from the claim text.