| First Author | Overturf K | Year | 1997 |
| Journal | Hum Gene Ther | Volume | 8 |
| Issue | 5 | Pages | 513-21 |
| PubMed ID | 9095403 | Mgi Jnum | J:40279 |
| Mgi Id | MGI:87624 | Doi | 10.1089/hum.1997.8.5-513 |
| Citation | Overturf K, et al. (1997) Adenovirus-mediated gene therapy in a mouse model of hereditary tyrosinemia type I. Hum Gene Ther 8(5):513-21 |
| abstractText | 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. |
