2022 Fiscal Year Final Research Report
Elucidation of neurodevelopmental disorder caused by CaMK2 mutant mice
Project/Area Number |
20K07423
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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 49030:Experimental pathology-related
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Research Institution | Hamamatsu University School of Medicine |
Principal Investigator |
Mutoh Hiroki 浜松医科大学, 医学部, 助教 (60443040)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Keywords | CaMK2β / ヒト疾患モデル動物 / 脳波異常 / 興奮性/抑制性のバランス |
Outline of Final Research Achievements |
Mouse models of human disease in which CaMK2β mutations were introduced, identified from patients with neurodevelopmental disorders, showed motor dysfunction and growth retardation similar to patients, and a remarkably decreased expression level of CaMK2β protein in the cerebellum. Furthermore, in the model mice, even a slight decrease in protein expression in the cerebral cortex and hippocampus was found to disrupt the excitatory/inhibitory balance of the neuronal circuitry and produce abnormal EEG. The disruption of the excitatory-inhibitory balance was also found to increase susceptibility to epilepsy. This study successfully established a mouse model of human disease in which CaMK2β mutations were introduced.
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Free Research Field |
神経生理学
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Academic Significance and Societal Importance of the Research Achievements |
本研究課題の成果により、CaMK2βが神経回路形成における興奮性・抑制性のバランス制御に必要である学術的に重要な発見をした。また、難治性神経疾患の患者より同定した変異を導入したヒト疾患モデルマウスの作出、機能解析することで病態の一端を解明することにも成功し、難治性疾患の病態解明と新たな薬剤開発や治療法につながることが期待される。
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