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The functional role of BRAF in cardiac development and bone formation

Research Project

Project/Area Number 15K19598
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Pediatrics
Research InstitutionTohoku University

Principal Investigator

Inoue Shin-ichi  東北大学, 医学系研究科, 助教 (70622091)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
KeywordsCFC症候群 / RASopathies / RAS/MAPKシグナル伝達経路 / BRAF / 先天性心疾患 / 疾患モデルマウス / 遺伝性疾患 / 線維化 / 筋線維芽細胞 / マウスモデル / イソプロテレノール / 肥大型心筋症 / 骨格形成異常 / 成長障害 / シグナル伝達 / 遺伝学 / 遺伝子 / 循環器
Outline of Final Research Achievements

Germline mutations in BRAF have been identified in 70% of patients with cardio-facio-cutaneous (CFC) syndrome, which is characterized by heart defects, distinctive facial features, short stature and ectodermal abnormalities. We recently demonstrated that mice expressing a Braf Q241R mutation on a C57BL/6J background are embryonic/neonatal lethal, with multiple congenital defects, preventing us from analyzing the phenotypic consequences after birth. Here, to further explore the pathogenesis of CFC syndrome, we backcrossed these mice onto an ICR genetic background. The BrafQ241R/+ ICR mice exhibited growth retardation, sparse and ruffled fur, a hunched appearance, craniofacial dysmorphism and heart defects, including pulmonary stenosis and atrial septal defects. These data suggest that the heterozygous BrafQ241R/+ ICR mice show similar phenotypes as CFC syndrome after birth and will be useful for elucidating the pathogenesis and potential therapeutic strategies for CFC syndrome.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (6 results)

All 2017 2016 2015

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (4 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Activated Braf induces esophageal dilation and gastric epithelial hyperplasia in mice2017

    • Author(s)
      Inoue Shin-Ichi、Takahara Shingo、Yoshikawa Takeo、Niihori Tetsuya、Yanai Kazuhiko、Matsubara Yoichi、Aoki Yoko
    • Journal Title

      Hum Mol Genet

      Volume: 26 Issue: 23 Pages: 4715-4727

    • DOI

      10.1093/hmg/ddx354

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Adult mice expressing a Braf Q241R mutation on an ICR/CD-1 background exhibit a cardio-facio-cutaneous syndrome phenotype.2015

    • Author(s)
      Moriya M, Inoue S, Miyagawa-Tomita S, Nakashima Y, Oba D, Niihori T, Hashi M, Ohnishi H, Kure S, Matsubara Y, Aoki Y.
    • Journal Title

      Hum Mol Genet.

      Volume: 24 Issue: 25 Pages: 7349-7360

    • DOI

      10.1093/hmg/ddv435

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] Cardio-facio-cutaneous症候群モデルマウスを用いた疾患・病態解明と治療法研究2017

    • Author(s)
      井上晋一、守谷充司、宮川-富田幸子、大場大樹、新堀哲也、中嶌八隅、橋美里、大西浩史、呉繁夫、松原洋一、青木洋子
    • Organizer
      第6回Multidisciplinary meeting on atherosclerosis
    • Related Report
      2017 Annual Research Report
  • [Presentation] がん原遺伝子Braf活性化はマウス食道の拡張、前胃上皮の過増殖をもたらす2017

    • Author(s)
      井上晋一、高原真吾、吉川雄朗、新堀哲也、谷内一彦、松原洋一、青木洋子
    • Organizer
      第40回分子生物学会年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Adult mice expressing a Braf Q241R mutation on an ICR/CD-1 background exhibit a cardio-facio-cutaneous syndrome phenotype2016

    • Author(s)
      Shin-ichi Inoue
    • Organizer
      The 13th International Congress of Human Genetics
    • Place of Presentation
      京都国際会館(京都)
    • Year and Date
      2016-04-03
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] がん原遺伝子BRAFの機能獲得性変異は先天性異常を引き起こす2015

    • Author(s)
      井上晋一
    • Organizer
      第38回日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド(神戸)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2022-11-04  

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