Analysis of susceptibility gene X using knock out rat aneurysm model

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K17979
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: Tokyo Women's Medical University
• Principal Investigator: Arai Naoyuki 東京女子医科大学, 医学部, 助教 (70868736)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 脳動脈瘤 / 遺伝子 / ラット / ノックアウト

Outline of Final Research Achievements

To clarify the contribution of susceptibility gene-X mediated cascade to the incidence or the enlargement of IAs, we subjected rats deficient in gene X or their littermates to the model of IAs previously established. IA formation at 4 bifurcation sites in the anterior circulation of the circle of Willis was examined using specimens harvested on the 14th day of IA induction. We found that the incidence of IAs was significantly exacerbated in heterozygous rats or ones deficient in gene X (1.75 times higher each, p<0.01) compared with that in wild type animals without influencing systemic blood pressure. Our study demonstrated for the first time that a loss of function variants in gene X might confer susceptibility to IAs.

Free Research Field

脳神経外科

Academic Significance and Societal Importance of the Research Achievements

次世代型シーケンサーを駆使した,頻度が低く効果サイズの高いレアバリアントの解析で特定された有望な脳動脈瘤感受性遺伝子Ｘについて、そのノックアウトラットモデルを用いて機能解析を行った。脳動脈瘤の発生率は、遺伝子欠損ラットで有意に高く、有望な候補遺伝子であることが明らかとなった。臨床で得られた候補遺伝子をin vivoの実験系で解析した研究は極めてまれであり、学術的意義は大きいと考える。