Association analysis with autism-like pathology using choroid plexus-specific CAMDI knockout mice

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07452
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Tokyo University of Pharmacy and Life Science
• Principal Investigator: Fukuda Toshifumi 東京薬科大学, 生命科学部, 講師 (50372313)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 脈絡叢 / 自閉症 / 発達障害 / 社会性 / 線毛 / 中心体 / CAMDI

Outline of Final Research Achievements

We generated choroid plexus-specific CAMDI knockout mice and analyzed their relationship with autism pathology by conducting histological and behavioral analyses. CAMDI reportedly stabilizes the microtubule and regulates centrosome maturation. As a result of the RNA-seq method, gene expression was decreased in "ciliary movement related to cell migration" and "microtubule-based movement". In addition, decreased expression of transthyretin, a differentiation/maturation marker, was observed. Behavioral analysis of choroid plexus-specific CAMDI knockout mice showed decreased social interaction and cognition.

Free Research Field

神経生物学

Academic Significance and Societal Importance of the Research Achievements

発達障害の要因として神経細胞の移動やスパインの形成に関与する蛋白質や抑制性神経やオリゴデンドロサイトの不全、脳内炎症などに着目した研究が多く主流である。胎生期の脈絡叢の成熟や脳実質への影響と発達障害を結びつける実験的な証明はほとんどなされていない。ヒトの臨床像から示唆される発達障害の要因について「脈絡叢の未成熟」の視点から取り組むことで、発達障害の病理に新しい知見をもたらすことが考えられる。