2021 Fiscal Year Final Research Report
A novel model animal recapitulating ALS pathophysiology
Project/Area Number |
19K08006
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 52020:Neurology-related
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Research Institution | National Center of Neurology and Psychiatry |
Principal Investigator |
Takahashi Yuji 国立研究開発法人国立精神・神経医療研究センター, 病院, 部長 (00372392)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Keywords | 筋萎縮性側索硬化症 / ErbB4 / コンディショナルノックアウトマウス / 運動神経細胞死 |
Outline of Final Research Achievements |
It is hypothesized that ErbB4 is essential for the survival of motor neurons and dysfunction of ErbB4 is a common pathology of ALS. To test the hypothesis in vivo, we generated tamoxiphen-dependent motor neuron-specific conditional knockout mice (cKO mice). In cKO mice, the appearance of clasping was observed 5 months after administration of tamoxiphen. Pathological analysis showed a 40% decrease in the number of spinal motor neurons 3 months after administration. The residual neurons maintained the stainability of ErbB4. We have obtained results supporting that ErbB4 is essential for the survival of mature spinal motor neurons and that cKO mice are model animals that recapitulate the pathophysiology of ALS.
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Free Research Field |
臨床神経学、臨床遺伝学、分子生物学
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Academic Significance and Societal Importance of the Research Achievements |
本研究により、ErbB4が運動神経細胞の生存に必須であることが明らかになり、ErbB4の機能低下性変異・ErbB4発現低下が運動神経細胞死の直接の原因になり得ることが示された。ALSの新たな病態機構の解明という学術的意義と共に、根本治療の開発に向けた創薬シーズ候補分子の同定という社会的意義も有すると考えられる。
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