| Project/Area Number |
19K08346
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 52050:Embryonic medicine and pediatrics-related
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| Research Institution | Tottori University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
檜垣 克美 鳥取大学, 研究推進機構, 准教授 (90294321)
難波 栄二 鳥取大学, 研究推進機構, 教授 (40237631)
足立 香織 鳥取大学, 研究推進機構, 助教 (50609237)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 福山型筋ジストロフィー / fukutin / 知的障害 |
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| Outline of Research at the Start |
福山型筋ジストロフィー（FCMD）症例は、筋症状だけでなく知的障害を認める。筋組織ではmTOR経路の異常があると考えられているが、中枢神経系でのmTOR経路の関与は不明である。本研究の目的は中枢神経症状へのmTOR経路異常の関与を解明し、治療法の開発に結びつけることである。方法は原因遺伝子のfukutin機能を失った疾患モデル神経細胞、中枢神経系のfukutin機能を失ったマウスを用いて大脳皮質形成異常を含む中枢神経障害の分子機構の解明、治療候補薬の効果の確認を行う。得られる知見はFCMDの中枢神経症状だけでなく、知的障害全体の治療研究に大きく貢献できると考えられる。
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| Outline of Final Research Achievements |
Central nervous system symptoms are known for Fukuyama congenital muscular dystrophy (FCMD). It is considered that the muscle tissue of FCMD model mice has a dysfunction of mTOR pathway, and there is a research report that administration of an mTOR inhibitor showed histological improvement of the muscle. It is possible that mTOR pathway dysfunction are also involved in FCMD central nervous system disorders, and the purpose of this study was to elucidate the involvement of mTOR pathway abnormalities in central nervous system and to link them to the development of therapeutic methods. We tried to elucidate the FKTN gene of SH-SY5Y cells by knocking it down with siRNA, but we could not demonstrate it by any method other than immunostaining. In addition to the possibility that there are no abnormalities in the central nervous system, problems with experimental subjects such as model cells were also raised as issues.
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| Academic Significance and Societal Importance of the Research Achievements |
中枢神経ではなく筋組織でmTOR異常を示した報告は新たにみられている（Experimental Physiology. 2020）。今回、福山型筋ジストロフィーの中枢神経症状におけるmTOR異常の関与につき細胞実験での実証を試みるも確認ができなかった。これまでの実験を踏まえ、モデル細胞等実験対象の検討が課題として挙がると考えている。
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