Molecular mechanism of autism caused by gene abnormalities of the clock genes

2019 Fiscal Year Final Research Report

• Project/Area Number: 16H05363
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Institute for Developmental Research Aichi Developmental Disability Center
• Principal Investigator: Nagata Koh-ichi 愛知県医療療育総合センター発達障害研究所, 分子病態研究部, 部長 (50252143)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 自閉性障害 / 時計遺伝子 / 大脳皮質発生 / 神経細胞

Outline of Final Research Achievements

Functional and structural defects in neuronal synapses are thought to underlie the pathophysiology of autism spectrum disorders (ASD). While more than 50 % of ASD patients suffer from sleep disturbance, relationship between circadian rhythm and ASD etiology is largely unknown. In this study, we focused on 3 circadian clock genes, TIMELESS, NR1D1 and PER3, whose gene abnormalities have been reported in ASD individuals. By the use of mouse models produced by "comprehensive in vivo/in vitro analytical battery" we constructed, we analyzed pathophysiological significance of gene abnormalities of TIMELESS, NR1D1 and PER3 in ASD.

Free Research Field

小児神経学

Academic Significance and Societal Importance of the Research Achievements

本研究は、概日リズム障害（時計遺伝子の機能障害）の観点からASDの大脳皮質形成障害・シナプス病態に迫り、新しい病態形成メカニズムの発見を目指した。この着想の発端は、ASD患者の遺伝子解析で、時計遺伝子TIMELESS, NR1D1 and PER3に新規ミスセンス変異を発見したことにある。これらの変異が大脳皮質形成とシナプス動態に与える影響をin vivo/in vitroで包括的に解析した結果、ASDの新たな病態メカニズムの存在が示唆された。