Elucidation of new physiological functions in the central nervous system of VRK1

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20742
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0802:Biomedical structure and function and related fields
• Research Institution: Oita University
• Principal Investigator: Umeda Ryohei 大分大学, 医学部, 助教 (90966300)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: VRK1 / zebrafish / 小頭症 / 運動機能異常 / 脳・神経 / 行動解析

Outline of Final Research Achievements

In this study, we focused on VRK1, one of the causative genes of neurodegenerative diseases characterized by microcephaly and motor dysfunction in humans, and aimed to elucidate the molecular mechanisms of VRK1-related microcephaly and motor dysfunction by generating and analyzing zebrafish lacking VRK1 (VRK1KO).
VRK1 deficiency caused a decrease in neurons, and we observed a decrease in locomotor activity and abnormal anxiety-like behavior. In particular, we showed that nuclear envelope abnormalities and increased heterochromatin in the zebrafish forebrain region, as well as a decrease in neuronal proliferation, including motor neurons, are likely to contribute to the pathological basis of diseases involving VRK1.

Free Research Field

神経変性疾患

Academic Significance and Societal Importance of the Research Achievements

本研究ではVRK1遺伝子欠損ゼブラフィッシュモデルを用いて小頭症および行動の異常などを認めた。さらに神経細胞における核膜形成の異常や神経増殖の減少など神経細胞に形態的な異常を認めた。以上より、VRK1が寄与する中枢神経系における小頭症や運動機能障害を特徴とする神経変性疾患に関連する病態基盤の一部を解明した。これまでにVRK1が寄与する小頭症や運動機能障害を特徴とする神経変性疾患のメカニズムについての報告はほとんどなく、本研究の結果はVRK1が関与する病態基盤の解明の一助となると示唆される。