1990 Fiscal Year Final Research Report Summary
Immunogenetical and Immunopathological Studies of Mechanisms of Fulminant Hepatitis in LEC Rats with Spontaneous Hepatits
| Project/Area Number |
01480162
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Experimental pathology
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| Research Institution | Hokkaido University |
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Principal Investigator |
TAKEICH Noritoshi Hokkaido Univ. Sch. of Med., Assosiate Professor, 医学部, 助教授 (40002133)
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| Co-Investigator(Kenkyū-buntansha) |
UNE Yoshie Hokkaido Univ. Sch. of Med., Instructor, 医学部, 講師 (60176716)
YOSHIDA Michihiro Hokkaido Univ. Faculty of Sch. Professor, 理学部, 教授 (60001765)
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| Project Period (FY) |
1989 – 1990
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| Keywords | Fulminant hepatitis / Animal model / LEC rats / Abnormal copper metabolism / Wilson's disease / Ceruloplasmin / Liver cirrhosis / Hepatoma |
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| Research Abstract |
LEC rats, a mutant inbred strain which was originally isolated from a closed colony of Long-Evans rats, develop acute hepatitis about 4 months after birth. Those rats which have survied acute hepatitis suffer from chronic hepatitis, and develop hepatocellular carcinomafrom one year after birth. The acute hepatitis resembles human fulminant hepatic failure both clinically and histopathologically, although genetic analyses have revealed that the hepatitis in inherited by autosomal recessive manner, the pathogenesis of hepatic disorders in LEC rat has not yet been clarified.
Recently we found that copper concentration in the liver of LEC rats was over 40 times that of normal LEA rats, while the serum ceruloplasmin and copper concentrations in LEC rats decreased significantly. The hepatocytes of LEC rats show steatosis in cytoplasm and pleomorphism of mitochondria, whichresemble the histologicfeatures of the liver in Wilson's disease. These findings suggest that the hereditary hepatitis in LEC rats is closely associated with copper toxicity. Thus the LEC rats will provide a unique and useful animal model for clarifying the mechanism of wilson's disease and finding teatment not only for Wilson's diseade but also other abnormal copper metabolism in human.
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