• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Novel animal model of cerebrovascular malformations

Research Project

Project/Area Number 22K16677
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 56010:Neurosurgery-related
Research InstitutionThe 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
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2023: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2022: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords脳海綿状血管奇形 / 脳血管奇形 / モデル動物 / 血管奇形
Outline of Research at the Start

脳血管奇形は中枢神経系に生じる異常血管の集簇であり、出血性脳卒中の原因として重要である。脳血管奇形においては、これまで家族性例の原因遺伝子異常の導入によりモデル動物が作製されてきた。一方ゲノム解析技術の向上に伴い、患者の多くを占める孤発性血管奇形症例において病因となる体細胞遺伝子変異の同定が近年もなされている。そこで本研究では、近年報告された脳血管内皮細胞を特異的に標的とするAAV (adeno-associated virus)を遺伝子導入用ベクターに用い、脳血管奇形原因遺伝子変異を導入することで、血管奇形の病態を高度に再現するモデル動物の作製を目指す。

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.

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。

Report

(3 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • Research Products

    (13 results)

All 2023 2022

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Open Access: 3 results) Presentation (5 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results)

  • [Journal Article] Clinical and Genetic Characteristics of Patients with Moyamoya Disease who Experienced Both Ischemic and Hemorrhagic Events2023

    • Author(s)
      Hirano Yudai、Miyawaki Satoru、Imai Hideaki、Hongo Hiroki、Teranishi Yu、Ishigami Daiichiro、Sakai Yu、Shimada Daisuke、Umekawa Motoyuki、Segawa Masafumi、Koizumi Satoshi、Ono Hideaki、Nakatomi Hirofumi、Saito Nobuhito
    • Journal Title

      World Neurosurgery

      Volume: 172 Pages: e438-e446

    • DOI

      10.1016/j.wneu.2023.01.047

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bypass Surgery for Adult-Onset Hemorrhagic Moyamoya Disease: Analysis Classified by Site of Initial Bleeding2023

    • Author(s)
      Hirano Yudai、Miyawaki Satoru、Imai Hideaki、Hongo Hiroki、Koizumi Satoshi、Yajima Hirohisa、Torazawa Seiei、Ishigami Daiichiro、Kiyofuji Satoshi、Saito Nobuhito
    • Journal Title

      World Neurosurgery

      Volume: 178 Pages: e585-e594

    • DOI

      10.1016/j.wneu.2023.07.130

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cerebrovascular Events During Treatment for Systemic Malignant Tumors in Patients with Moyamoya Disease2023

    • Author(s)
      Ogawa Shotaro、Miyawaki Satoru、Imai Hideaki、Hongo Hiroki、Umekawa Motoyuki、Kiyofuji Satoshi、Ishigami Daiichiro、Sakai Yu、Torazawa Seiei、Hirano Yudai、Koizumi Satoshi、Saito Nobuhito
    • Journal Title

      World Neurosurgery

      Volume: 179 Pages: e314-e320

    • DOI

      10.1016/j.wneu.2023.08.083

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hypertensive disorders of pregnancy in moyamoya disease: A single institution experience2023

    • Author(s)
      Yajima Hirohisa、Miyawaki Satoru、Sayama Seisuke、Kumasawa Keiichi、Ikemura Masako、Imai Hideaki、Hongo Hiroki、Hirano Yudai、Ishigami Daiichiro、Torazawa Seiei、Kiyofuji Satoshi、Koizumi Satoshi、Saito Nobuhito
    • Journal Title

      Journal of Stroke and Cerebrovascular Diseases

      Volume: 32 Issue: 11 Pages: 107377-107377

    • DOI

      10.1016/j.jstrokecerebrovasdis.2023.107377

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Symptomatic and Stenotic Developmental Venous Anomaly with Pontine Capillary Telangiectasia: A Case Report with Genetic Considerations2022

    • Author(s)
      ISHIGAMI Daiichiro、KOIZUMI Satoshi、MIYAWAKI Satoru、HONGO Hiroki、TERANISHI Yu、MITSUI Jun、SAITO Nobuhito
    • Journal Title

      NMC Case Report Journal

      Volume: 9 Issue: 0 Pages: 139-144

    • DOI

      10.2176/jns-nmc.2022-0022

    • ISSN
      2188-4226
    • Year and Date
      2022-12-31
    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genome-Wide Association Study of Intracranial Artery Stenosis Followed by Phenome-Wide Association Study2022

    • Author(s)
      Dofuku S, Sonehara K, Miyawaki S, Sakaue S, Imai H, Shimizu M, Hongo H, Shinya Y, Ohara K, Teranishi Y, Okano A, Ono H, Nakatomi H, Teraoka A, Yamamoto K, Maeda Y, Nii T, Kishikawa T, Suzuki K, Hirata J, Takahashi M, Matsuda K, Kumanogoh A, Matsuda F, Okada Y, Saito N.
    • Journal Title

      Transl Stroke Res.

      Volume: - Issue: 3 Pages: 322-333

    • DOI

      10.1007/s12975-022-01049-w

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Somatic GJA4 gain-of-function mutation in orbital cavernous venous malformations2022

    • Author(s)
      Hongo Hiroki、Miyawaki Satoru、Teranishi Yu、Mitsui Jun、Katoh Hiroto、Komura Daisuke、Tsubota Kinya、Matsukawa Takashi、Watanabe Masakatsu、Kurita Masakazu、Yoshimura Jun、Dofuku Shogo、Ohara Kenta、Ishigami Daiichiro、Okano Atsushi、Kato Motoi、Hakuno Fumihiko、Takahashi Ayaka、Kunita Akiko、Ishiura Hiroyuki、et al.
    • Journal Title

      Angiogenesis

      Volume: 26 Issue: 1 Pages: 37

    • DOI

      10.1007/s10456-022-09846-5

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genetics of brain arteriovenous malformations and cerebral cavernous malformations2022

    • Author(s)
      Hongo Hiroki、Miyawaki Satoru、Teranishi Yu、Ishigami Daiichiro、Ohara Kenta、Sakai Yu、Shimada Daisuke、Umekawa Motoyuki、Koizumi Satoshi、Ono Hideaki、Nakatomi Hirofumi、Saito Nobuhito
    • Journal Title

      Journal of Human Genetics

      Volume: 68 Issue: 3 Pages: 157-167

    • DOI

      10.1038/s10038-022-01063-8

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 脳および眼窩内海綿状血管奇形の体細胞遺伝子変異解析2023

    • Author(s)
      本郷 博貴, 宮脇 哲, 寺西 裕, 堂福 翔吾, 小原 健太, 石神 大一郎, 岡野 淳, 三井 純, 加藤 洋人, 栗田 昌和, 渡邉 正勝, 辛 正廣, 中冨 浩文, 後藤 浩, 石川 俊平, 齊藤 延人.
    • Organizer
      第52回日本脳卒中の外科学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 脳・眼窩内血管奇形の遺伝子解析研究2023

    • Author(s)
      本郷 博貴, 宮脇 哲, 寺西 裕, 堂福 翔吾, 小原 健太, 石神 大一郎, 岡野 淳, 清藤 哲史, 三井 純, 栗田 昌和, 渡邉 正勝, 辛 正廣, 中冨 浩文, 後藤 浩, 石川 俊平, 齊藤 延人.
    • Organizer
      第81回日本脳神経外科学会総会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 眼窩内海綿状血管奇形関連遺伝子変異の同定2022

    • Author(s)
      本郷 博貴, 宮脇 哲, 栗田 昌和, 加藤 基, 寺西 裕, 堂福 翔吾, 小原 健太, 石神 大一郎, 岡野 淳, 三井 純, 加藤 洋人, 渡邉 正勝, 辛 正廣, 中冨 浩文, 後藤 浩, 石川 俊平, 岡崎 睦, 齊藤 延人
    • Organizer
      第18回日本血管腫血管奇形学会学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] 眼窩内海綿状血管奇形における新規関連遺伝子変異の同定2022

    • Author(s)
      本郷 博貴, 宮脇 哲, 寺西 裕, 堂福 翔吾, 小原 健太, 石神 大一郎, 岡野 淳, 三井 純, 加藤 洋人, 栗田 昌和, 渡邉 正勝, 辛 正廣, 中冨 浩文, 後藤 浩, 石川 俊平, 齊藤 延人
    • Organizer
      日本脳神経外科学会 第81回学術総会
    • Related Report
      2022 Research-status Report
  • [Presentation] Epidemiology/etiology of cerebral cavernous malformations2022

    • Author(s)
      Hiroki Hongo, Satoru Miyawaki, Nobuhito Saito
    • Organizer
      10th European-Japanese Cerebrovascular Congress
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research / Invited

URL: 

Published: 2022-04-19   Modified: 2025-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi