Investigation of the mechanism causing sex differences in ASD

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K06901
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 46020:Anatomy and histopathology of nervous system-related
• Research Institution: Toyo University
• Principal Investigator: Ohtani-Kaneko Ritsuko (大谷律子) 東洋大学, 生命科学部, 教授 (00161183)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 自閉症 / 雌雄差 / Crmp4欠損マウス / 超音波発声 / モデルマウス

Outline of Final Research Achievements

Suitable models to analyze sex differences in ASD pathogenesis remain insufficient. In this study, we performed experiments using autism model mice (Collapsin mediator protein 4 deficiency (KO) mice) that have characteristics of "impaired sociality" and "sensory abnormalities" in a male-predominant manner. We recorded isolation-induced ultrasonic vocalizations (USVs) emitted from wild-type (WT) and KO littermates, classified USVs into 10 types, and compared the number of USVs in each type by genotypes and sex. We found male KO mice exhibited a reduction in the total number of USVs and most of those USV types. We therefore got a suitable ASD animal model and tool for assessing sex-based communication deficits during the early postnatal period. Although the results obtained from steroid exposure experiments were severely different among individuals and could not reveal significant effects, transcriptome analysis revealed genes with differences in expression between sexes in KO mice.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

自閉症には出現頻度や症状に性差が存在する。自閉症男児患者のwhole-exome sequencing 解析により、Crmp4遺伝子の1塩基置換のみを持つ事例を見出した。さらにCrmp4欠損（KO）マウスには雌雄差のある社会性行動の低下や感覚異常が現れること、KOや点変異により樹状突起形成が異常になることを報告した。今回は自閉症発症の早期検証に使える超音波発声パターン分類報告や、トランスクリプトーム解析による雌雄差形成候補遺伝子を報告した。KOマウスのこれらの知見は、自閉症発症や雌雄差形成メカニズムに繋がる重要な情報であり、自閉症研究や予防法開発にとって重要なものとして社会的意義が高い。