Novel animal model of cerebrovascular malformations

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K16677
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: The University of Tokyo
• Principal Investigator: Hongo Hiroki 東京大学, 医学部附属病院, 助教 (80908682)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 脳海綿状血管奇形

Outline of Final Research Achievements

Cerebrovascular malformations are clusters of abnormal blood vessels in the central nervous system. Animal models of the disease have been generated by introducing gene mutations identified as germline mutations in familial cases, but these models alone have not fully explained the pathophysiology. In this study, Mice in which the GJA4 mutation, which was newly identified as a somatic mutation in intraorbital cavernous vascular malformations in a previous study, was introduced specifically into vascular endothelial cells, were generated. Mice transgenic with LoxP-stop-LoxP-mutant Gja4 (floxed mice) were generated, and these were crossed with Tie2-Cre mice, a kind of vascular endothelial cell-specific Cre mice. It was found that mice expressing mutant Gja4 were embryonic lethal.

Free Research Field

脳血管疾患

Academic Significance and Societal Importance of the Research Achievements

本研究はGja4変異が血管内皮細胞に対して有害であることを示唆し、GJA4変異が血管奇形の直接の原因となっている可能性を支持するものと考えられた。今後詳細な組織学的解析や分子生物学的な解析を行うことにより、血管奇形の形成に関わる詳細な病態の解明、延いては新規治療法の開発につながる知見の獲得が可能となることが期待された。