| Project/Area Number |
18K19509
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 52:General internal medicine and related fields
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Project Period (FY) |
2018-06-29 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
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| Keywords | トランスジェニックマウス / 自閉症 / 大人の発達障害 |
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| Outline of Final Research Achievements |
Here we show that reduced expression of CHD8 in oligodendrocytes gives rise to abnormal behavioral phenotypes in mice. CHD8 was found to regulate the expression of many myelination-related genes and to be required for oligodendrocyte maturation and myelination. Ablation of Chd8 specifically in oligodendrocytes of mice impaired myelination, slowed action potential propagation, and resulted in behavioral deficits including increased social interaction and anxiety-like behavior, with similar effects being apparent in Chd8 heterozygous mutant mice. Our results thus indicate that CHD8 is essential for myelination and that dysfunction of oligodendrocytes as a result of CHD8 haploinsufficiency gives rise to several neuropsychiatric phenotypes.
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| Academic Significance and Societal Importance of the Research Achievements |
CHD8の欠損によりオリゴデンドロサイトの機能が障害することが判明したため、オリゴデンドロサイト特異的CHD8ヘテロ欠損マウスを作製し行動解析を行ったところ、自閉症様行動の一部が再現されることが判明した。すでにわれわれは、遺伝学的な手法および再ミエリン化薬剤の投与による治療の実験を進めており、自閉症の治療法への応用について検討している。これらの知見は当初の研究目的に適っており、順調に達成されつつあると考えられる。
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