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Hum Gene Ther. 1997 Mar 20;8(5):513-21.

Adenovirus-mediated gene therapy in a mouse model of hereditary tyrosinemia type I.

Author information

1
Medical and Molecular Genetics Department, Oregon Health Sciences University, Portland 97201, USA.

Abstract

Mice lacking the enzyme fumarylacetoacetate hydrolase (FAH) have symptoms similar to humans with the disease hereditary tyrosinemia type I (HT1). FAH-deficient mice were injected with a first-generation adenoviral vector expressing the human FAH gene and followed for up to 9 months. Nontreated FAH mutant control mice died within 6 weeks from fulminant liver failure, whereas FAH adenovirus-infected animals survived until sacrifice at 2-9 months. Nine of 13 virus-treated animals developed hepatocellular cancer. Immunohistochemical analysis revealed a mosaic of FAH-deficient and FAH-positive cells in all animals and liver function tests were improved compared to controls. Even mice harvested 9 months after viral infection had > 50% FAH-positive cells. These results demonstrate the strong selective advantage of FAH-expressing cells in an FAH-deficient liver but also illustrate the danger of carcinomas arising from FAH-deficient hepatocytes in HT1.

PMID:
9095403
DOI:
10.1089/hum.1997.8.5-513
[Indexed for MEDLINE]

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