| Project/Area Number |
20K16671
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 52030:Psychiatry-related
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| Research Institution | Kagoshima University |
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Principal Investigator |
SAKIMOTO Hitoshi 鹿児島大学, 医歯学域鹿児島大学病院, 客員研究員 (80813667)
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| Project Period (FY) |
2020-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2023: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2022: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2021: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 有棘赤血球舞踏病 / てんかん / 症状修飾因子 / モデルマウス / 症状誘発因子 / ChAcモデルマウス / VPS13A / chorein |
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| Outline of Research at the Start |
有棘赤血球舞踏病モデルマウスでてんかん発作を生じる個体が複数確認され、てんかんを誘発する機能をもつ遺伝子変異が突然変異で生じたことが強く示唆された。てんかんを誘発すると考えられる遺伝子を同定したため、同遺伝子がてんかん誘発に関与していることの再確認と、同遺伝子の産物である蛋白質の解析を行い、病態への関与を解明する。また、他の神経変性疾患でのてんかん誘発に関与をしていないか、確認を行う。
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| Outline of Final Research Achievements |
Chorea-acanthocytosis (ChAc) is a human, autosomal recessive neurodegenerative disorder. Clinically, ChAc is characterized by adult-onset chorea, acanthocytosis in erythrocytes, and epilepsy (40%). Humans with ChAc also exhibit a range of ages of onset and symptoms, even in the same family lineage. Similarly, the behavioral and pathological phenotypes of the model mice varied a good deal from individual to individual, indicating that differences between individuals. Several ChAC model mice with epilepsy appeared in the same family lineage. It is probable that genetic modifiers affect the epilepsy of the disease phenotypes. Occurrence of de novo mutations which is modifying factors for epilepsy was suggested, and genetic analysis identified the mutation of Hnrnpm. ChAc model mouse with Hnrnpm mutation tended to have epileptic seizures.
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| Academic Significance and Societal Importance of the Research Achievements |
症状修飾因子を分子遺伝学的に証明した報告は殆ど無い。症状修飾因子として遺伝子変異の同定に至った研究は極めて少なく、学術的独自性は高い。変異同定とともに分子的機能病態まで明らかにできれば、神経変性疾患に伴うてんかん発作や加齢に伴い合併する高齢てんかんの病因について新たな側面を提示できることになり、実臨床的にも意義深く創造性も高いと考えている。
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