The effect of circadian genes to Autism and neuron development

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K08265
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Jichi Medical University
• Principal Investigator: MATSUMOTO Ayumi 自治医科大学, 医学部, 准教授 (20458318)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 概日リズム / 自閉スペクトラム症 / 発達障害 / 知的障害 / Timeless

Outline of Final Research Achievements

In order to clarify the influence of circadian rhythm genes on autism spectrum disorder and its mechanism, behavioral analysis was performed using Timeless KO mice. The results suggested a decline in sociality, consistent with ASD. Furthermore, analysis using neural activity markers detected differences between Timeless KO mice and WT mice, and the results are currently in preparation for submission. It was suggested that Timeless may be involved in ASD, particularly in the decline in sociality, and new knowledge was gained about the pathogenesis of ASD.
In addition, exome analysis was performed on 38 patients with developmental disorders and intellectual disabilities, including ASD, and a diagnosis was made in 12 cases. Functional solutions for GAP43 and CACNA1H have been added and are currently in preparation for submission.

Free Research Field

小児神経

Academic Significance and Societal Importance of the Research Achievements

Timelessはこれまでヒト、マウスにおける概日リズム、ASDのエビデンスが乏しかったが、マウスでの行動解析および脳での活動性をみることでASDとの関連を明らかにした。ASD、概日リズムの病態解明につなげることができた。また、Timeless K.O.マウスは今後内服の治療効果判定に用いることも可能となり、今後の発展、社会的な意義は非常に大きい。エクソーム解析においても多数の診断や、GAP43など疾患報告のない遺伝子について疾患との関連を見出すことができ、患者さんや社会にとって非常に大きな意義があったと考えている。今後、解析を継続することでより詳細な病態解明につなげていきたい。