2021 Fiscal Year Final Research Report
Molecular Mechanisms of Neurodevelopmental Disorders mediated by the Synapse Adhesion Molecule LRFN2
| Project/Area Number |
19K06905
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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 46010:Neuroscience-general-related
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
MORIMURA NAOKO 滋賀医科大学, 医学部, 特任助教 (00349044)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | シナプス接着分子 / 発達障害 / 非ヒト霊長類 |
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| Outline of Final Research Achievements |
LRFN2, a synaptic adhesion molecule that regulates the structure and function of excitatory synapses, has been shown to cause human autistic-like and schizophrenic-like behavioral and synaptic abnormalities in knockout mice. In this research project, we started to develop LRFN2 knockout crab-eating macaques by CRISPR/Cas9 genome editing technology in order to examine the mechanism of neurodevelopmental disorders in the primate brain. In addition, nuclear magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) were performed to elucidate the structure and axon running in the developing brain of the normal crab-eating macaque.
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| Free Research Field |
神経科学
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| Academic Significance and Societal Importance of the Research Achievements |
自閉症や統合失調症などの発達障害とシナプス接着分子の関連性を示す研究報告の蓄積から、近年、シナプス異常と発達障害の因果関係が支持されている。マウス（齧歯類）を用いた研究から多くの発見が見出されている一方で、ヒト（霊長類）との脳構造や機能における進化的な差が大きいために治療法に結びかない現状がある。興奮生シナプスの制御に関わり、かつ自閉症や統合失調症の患者に変異が認められているLRFN2遺伝子欠損非ヒト霊長類サルが作出されることにより、基礎知見と臨床応用を結ぶ橋渡しができるものと期待される。
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