Hydrocephalus and Dementia due to motile cilia dysfunction

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H03591
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: Nagasaki University
• Principal Investigator: Yoshiura Koh-ichiro 長崎大学, 原爆後障害医療研究所, 教授 (00304931)
• Co-Investigator(Kenkyū-buntansha): 辻野 彰 長崎大学, 病院(医学系), 教授 (70423639)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: CFAP43 / 正常圧水頭症 / 変異解析 / モデルマウス / 発現解析

Outline of Final Research Achievements

Ependymal cells of CFAP43 gene knockout mice (KO mice) were collected by microdissection method, cDNA library was synthesized, and expression analysis was performed using a next-generation sequencer. KO mice and control mice were clearly distinguished on classification, and ontology analysis using genes with altered expression levels revealed altered expression of gene clusters related to ensheathment of neuron, telencephalon development, and negative regulation of cell differentiation.
Analysis of mutations in 96 genes construction cilia in patients with normal pressure hydrocephalus revealed truncation-type mutations with a minor allele frequency <0.01 in the general population, including the DRC1 gene, in 5 genes, and missense mutations in 19 genes.

Free Research Field

分子遺伝学

Academic Significance and Societal Importance of the Research Achievements

線毛関連遺伝子の変異は，水頭症発生に関与することが明確に示された。上衣細胞の機能異常は神経分化関連の遺伝子群に集中し，線毛の構造異常から分化異常に至り機能不全に陥っていることが示唆された。ただし，その詳細は今後の研究を待たざるをえない。
線毛関連遺伝子の変異が，正常圧水頭症患者に多く見つかっていることは，正常圧水頭症・水頭症・認知症患者の一部が，線毛関連遺伝子異常症であることを明確に示唆しており，成人あるいは初老期に発症する遺伝病であることを世に知らしめた意義は大きい。