| Project/Area Number |
11470061
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Nihon University |
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Principal Investigator |
ESUMI Mariko Nihon University School of Medicine, Associate Professor, 医学部, 助教授 (30167291)
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| Co-Investigator(Kenkyū-buntansha) |
HIOKI Kohji Central Laboratories for Experimental Animals, Chief, 実験動物中央研究所, 室長
KUSUMI Yoshiaki Nihon University School of Medicine, Lecturer, 医学部, 講師 (60186393)
UNO Masatsune Nihon University School of Medicine, Associate Professor, 医学部, 助教授 (30150709)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥13,400,000 (Direct Cost: ¥13,400,000)
Fiscal Year 2001: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2000: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1999: ¥8,500,000 (Direct Cost: ¥8,500,000)
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| Keywords | Hepatitis C virus / Hepatocellular carcinoma / Transgenic mouse / Albumin promoter / SRα promoter / Srαプロモーター |
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| Research Abstract |
1 Expression analysis of transgenic mice
We analyzed 5 lines of transgenic mice carrying the whole genome of hepatitis C virus (HCV); A44, A39 and A48 were controlled under the mouse albumin enhancer/ promoter; S2 and S5 were under the SR_α promoter. The HCV mRNA was expressed in the liver of one of 17 A44 at the age of 12 months and 12 of 17 A44 at the age of 21 months. All mice of A39 and A48 expressed the HCV transgene in the liver, but both S2 and S5 did not. The mRNA was 9.4 kb in length, and the real-time PCR revealed that 50 to 4000 copies of HCV RNA were expressed in 1 μg of total RNA. The expression of HCV mRNA seemed to be localized in the liver tissue. Less than the detection limit of HCV core protein (5 pg/mg protein) was detected in the liver. These transgenic mice A39, A44 and A48 showed the similar level of HCV expression to that of patients with chronic hepatitis C, that is different from other transgenic mice with the high level of HCV expression.
2 Histological examinat
… More
ion of transgenic mouse liver
Inflammatory cell infiltration and spotty necrosis were observed in transgenic mouse liver of A39, A44 and A48. The number of spotty necrosis foci was significantly higher in A39 and A44 than non-transgenic mice at the age of 21 months. The fatty change of liver was not significant between transgenics and non-transgenics. Liver fibrosis and tumorous lesion were not observed until 21 months old. HCV antibodies were not detected in serum of the mice.
3 Molecular pathogenesis of transgenic mouse liver
Real-time RT-PCR of mRNA revealed that mRNAs such as interferon-inducible genes and cell cycle-related genes were up-regulated in transgenic mouse liver, that is observed in patients with HCV infection.
Thus, these transgenic mice were similar to patients with weak hepatitis. Anti-viral immune response of the mice, however, was so much less than that of patients, suggesting that the introduction of anti-viral immune system to these HCV transgenic mice should be required for establishing a model of hepatocarcinogenesis. Less
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