| Project/Area Number |
21591095
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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 |
Neurology
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| Research Institution | Kagoshima University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
有村 公良 鹿児島大学, 大学院・医歯学総合研究科, 准教授 (30140908)
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| Research Collaborator |
HIRANO Ryuki 鹿児島大学, 医学部・歯学部附属病院, 医員
NAKAMURA Tomonori 鹿児島大学, 大学院・医歯学総合研究科, 大学院生
HASHIGUCHI Akihiro 鹿児島大学, 医学部・歯学部附属病院, 医員
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2011: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
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| Keywords | SCAN1 / Tdp1 / SSBR / 末梢神経障害 / 一本鎖DNA修復 / ノックアウトマウス / DNA repair / 一本鎖DNA修 |
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| Research Abstract |
Spinocerebellar ataxia with axonal neuropathy(SCAN1) is an autosomal recessive disorder characterized by ataxia, cerebellar atrophy, and peripheral neuropathy. We found SCAN1 is caused by a specific point mutation the tyrosyl-DNA phosphodiesterase(TDP1) gene. Functional and genetic studies suggest that this mutation, which disrupts the active site of the Tdp1 enzyme, causes disease by a combination of decreased catalytic activity and stabilization of the normally transient covalent Tdp1-DNA intermediate. The Tdp1 knockout mice showed the retinitis pigmentosa like phenotype. The RNA expressions were mostly normal in the microarray studies of Tdp1 knockout mice. These findings make spurred understanding of DNA repair in human biology and suggested a novel mechanism of human disease.
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