| Project/Area Number |
06670522
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Gastroenterology
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| Research Institution | University of Tokyo |
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Principal Investigator |
KOIKE Kazuhiko Tokyo University, Faculty of Medicine, Assistent Proffessor, 医学部(病), 助手 (80240703)
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| Co-Investigator(Kenkyū-buntansha) |
MORIYA Kyoji Tokyo University, Faculty of Medicine, Assistan, Proffesso, 医学部(病), 助手
YOTSUYANAGI Hiroshi Tokyo University, Faculty of Medicine, 医学部(病), 医員 (30251234)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1994: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | hepatitis C virus / envelope proteins / transgenic mice / hepatitis / hepatocellular carcinoma / vaccine |
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| Research Abstract |
In an attempt to establish a model for hepatitis C virus infection, we produced transgenic mice by introducing the hepatitis C virus envelope genes, E1 and E2, under the control of a regulatory element from hepatitis B virus. F1-generation mice from the established founders demonstrated expression of both E1 and E2 proteins as glycosylated forms in their organs including the liver. Immunostaining revealed the localization of envelope proteins principally in the cytoplasm of hepatocytes around the hepatic central veins. Furthermore, E1 and E2 proteins were shown by immunoprecipitation to be associated with each other in the mouse liver. There was no evidence of tissue pathology in the mouse liver up to 16 months of age, suggesting that E1 and E2 proteins per se may not have direct pathogenic effects. Our results demonstrate the first successful expression of hepatitis C vircus gene products in the mouse liver and the association of in vivo expressed HCV envelope proteins. This transgenic mouse would be a good model to study the virus-cell interactions of HCV such as intracellular transport and assembly of envelope proteins. Also it may be a good model system to determine the role of these proteins in the pathogenesis of hepatitis or extra-hepatic manifestations in HCV infection with the introduction of cytotoxic T lymphocytes specific for the envelope proteins.
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