| Project/Area Number |
17K07094
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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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| Research Field |
Nerve anatomy/Neuropathology
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| Research Institution | Nagoya University |
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Principal Investigator |
Ito Mikako 名古屋大学, 医学系研究科, 特任講師 (60444402)
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| Co-Investigator(Kenkyū-buntansha) |
大河原 美静 名古屋大学, 医学系研究科, 准教授 (80589606)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 先天性筋無力症候群 / GFPT1 / iPS / 先天性筋無力症行群 / 神経筋接合部 / 細胞・組織 / 神経科学 / 再生医学 |
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| Outline of Final Research Achievements |
One of the causative molecules of congenital myasthesis syndrome (CMS) is a mutation in GFPT1, a glycosylation enzyme of proteins and lipids, which is characterized by limb-type muscle weakness. GFPT1-L isoform is formed in skeletal muscle and enzyme activity is reduced. In this study, in order to clarify the role of GFPT1-L in skeletal muscle, model mouse Gfpt1-L-/-was prepared and phenotypic analysis was performed.
In addition, we identified the GFPT1 c.722 ^ 723insG mutation in CMS patients and prepared a model mouse of the mutation. The mice were decreased motor function, decreased amount of glycosylated protein, fragmentation of AChR cluster, muscle atrophy, and increased interstitial space. of muscle fiber. It showed a patient-like phenotype.
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| Academic Significance and Societal Importance of the Research Achievements |
先天性筋無力症候群は指定難病の対象となっており、全身の筋力低下， 易疲労性を呈し，生後 1 年以内に発症することが多い稀な疾患である。神経筋接合部を構成する遺伝子検査を実施し、変異が発見された場合は、CMSの原因となりうる変異かどうかを精査する必要がある。本研究では先天性筋無力症候群患者において、GFPT1内に複合ヘテロ変異を同定した。GFPT1の神経筋接合部での機能は不明な点が多く、GFPT1の骨格筋でのisoformについて調査した。また、患者変異を保有するマウスを作成し、病態の詳細な解析を行った。今後、治療薬のスクリーニング、治療法の開発へ応用できると期待している。
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