| Project/Area Number |
09358018
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Laboratory animal science
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| Research Institution | Tokyo Metropolitan Organization for Medical Research |
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Principal Investigator |
YONEKAWA Hiromichi Tokyo Metropolitan Organization for Medical Research, The Tokyo Metropolitan Institute of Medical Science, Vice-Director, 東京都臨床医学総合研究所, 副所長 (30142110)
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| Co-Investigator(Kenkyū-buntansha) |
TSUCHIYA Masayuki Chugai Pharmaceutical Co. LTD, Researcher, 探索研究所, 研究員
KOIKE Morio The Tokyo metropolitan Komagome Hospital, Department of Pathology, Head, 病理科, 部長
KOHARA Michinori Tokyo Metropolitan Organization for Medical Research, The Tokyo Metropolitan Institute of Medical Science, Researcher, 東京都臨床医学総合研究所, 研究員 (10250218)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥25,800,000 (Direct Cost: ¥25,800,000)
Fiscal Year 1999: ¥7,500,000 (Direct Cost: ¥7,500,000)
Fiscal Year 1998: ¥8,300,000 (Direct Cost: ¥8,300,000)
Fiscal Year 1997: ¥10,000,000 (Direct Cost: ¥10,000,000)
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| Keywords | Hepatitis C Virus (HCV) / Transgenic mice / Cre / loxP conditional expression / Mechanism for viral exclusion / Animal Models / C型肝炎ウイルス(HCV) / ウイルス排除機構 / C型肝炎 / 遺伝子導入動物 / マウス / ヒト疾患モデル / 病理性発現機序 / 細胞障害性T細胞 |
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| Research Abstract |
The hepatitis C virus (HCV) is the major causative agent of non-A/non-B hepatitis. A major characteristic of HCV infection is the extremely high (up to 80%) risk of chronicity; in addition, chronic infection of HCV can frequently leads to liver cirrhosis and hepatocellular carcinoma. An important issue regarding the pathogenesis of HCV-associated liver lesions is to determine whether HCV proteins might have a direct effect on cellular phenotype. however, little was known about this respect. To address this question, we tried to establish animal model for HCV. Introducing an efficient Cre/loxP conditional transgenesis, we created several lines of transgenic mice with HCVcDNA (nucleotides 294-3435). After administration of adenovirus that expresses Cre recombinase, the HCV genome introduced as a transgene can express several HCV-specific core proteins in most hepatocytes of the transgenic mice. Moreover, pathological changes and elevated level of serum alanine animotransferase suggested that liver injury occurred in the transgenic mice that express the HCV transgene. A CD4 and CD8 positive cells depletion assay normalized both the serum alanine aminotransferase increases and the pathological changes in the liver. These results suggested that HCV proteins are not directly cytopathic and that the host immune response plays a pivotal role in HCV infection. Thus, this HCV cDNA transgenic mouse provides a powerful tool with which to investigate the immune responses and pathogenesis of HCV infection.
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