| Project/Area Number |
11680816
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Laboratory animal science
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| Research Institution | Tohoku University |
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Principal Investigator |
MIYOSHI Ichiro Tohoku University, Graduate School of Medicine, Research Associate, 大学院・医学系研究科, 助手 (10183972)
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| Co-Investigator(Kenkyū-buntansha) |
OKAMURA Tadashi Tohoku University, Graduate School of Medicine, Research Associate, 大学院・医学系研究科, 助手 (00333790)
KASAI Noriyuki Tohoku University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (60001947)
高橋 一広 東北大学, 大学院・医学系研究科, 助手 (20292427)
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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 |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1999: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | Prion / Transgenic / EGFP / Model mouse / Molecular interaction |
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| Research Abstract |
We attempted to establish the model mice, which were highly susceptible for human prion and enabled the visualization of molecular interaction of prion protein (PrP) in vivo, especially conversion of normal cellular PrP into abnormal prion (PrPsc) by transgenic techniques. The constructs were designed to encode the fusion protein composed of chimeric protein which was composed of N-terminal sequences from mouse and main ORF region from human PrPc and Fluorescent protein (FP). As C-terminal sequences were deleted from human PrPc, the fusion protein derived from the transgene was expected to be secretary form. Four (EGFP-mouse/human chimeric PrP) and five (EBFP-mouse/human chimeric PrP) transgenic lines were produced. The transgenic mice showed expression of the transgene in the general organs, and high expression in the brain. Both the level of transgene expression and 1he processing of gene products was expected to be similar to that of endogenous mouse prion, as the regulatory region of the transgene were derived from mouse genome. Unfortunately, this project was suspended as inoculation of PrPsc revealed that the transgenic mice carrying the transgene encoding secretary mouse/human chimeric PrP were not susceptible for human prion in our latest collaborative study [Kitamoto (Tohoku University), Mohri (Kyushu University) and Miyoshi, unpublished data]. Our previous collaborative study indicated the mice expressing mouse/human chimeric PrP was highly susceptible to human prion [Kitamoto (Tohoku University), Mohri (Kyushu University) and Miyoshi, unpublished data], however, modification of the molecule into secretary form was not effective to enhance the susceptibility.
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