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The pathogenesis of MIRAGE syndrome revealed by model mice using genome editing

Research Project

Project/Area Number 18K08527
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 54040:Metabolism and endocrinology-related
Research InstitutionKeio University

Principal Investigator

Hasegawa Tomonobu  慶應義塾大学, 医学部(信濃町), 教授 (20189533)

Co-Investigator(Kenkyū-buntansha) 高田 修治  国立研究開発法人国立成育医療研究センター, システム発生・再生医学研究部, 部長 (20382856)
鳴海 覚志  国立研究開発法人国立成育医療研究センター, 分子内分泌研究部, 室長 (40365317)
石井 智弘  慶應義塾大学, 医学部(信濃町), 准教授 (70265867)
天野 直子  慶應義塾大学, 医学部(信濃町), 共同研究員 (70348689)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsMIRAGE症候群 / ゲノム編集 / モデルマウス / 表現型 / 病理所見
Outline of Final Research Achievements

MIRAGE syndrome is characterized by myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotype, and enteropathy, caused by mutation in SAMD9. We generated MIARGE syndrome model mice using genome editing, CRISPR/Cas9 system. In model mice, the expression of mutant SAMD9 by tamoxifen treatment induced the following phenotypes. 1.shortening in the life span, 2. poor weight gain in surviving mice, 3. histological abnormalities in thymus, spleen, ovary, intestine, kidney, pancreas, bone marrow, cerebral cortex, heart, and adrenal.

Academic Significance and Societal Importance of the Research Achievements

本研究の学術的意義は以下の通りである。すなわち、世界で初めてMIRAGE症候群(以下本症候群)のモデルマウスの作成に成功した。モデルマウスにより本症候群のin vivo病態解析が進む。既に本研究により、本症候群に認められる臨床症状からの予想を上回る極めて多彩な臓器の組織学的変化が明らかとなった。今後、細胞レベル、遺伝子発現レベルでの解析が期待される。また治療法のない本症候群に対するin vivo薬物スクリーニングが可能となった。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (10 results)

All 2021 2020 2019 2018

All Journal Article (4 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (6 results) (of which Int'l Joint Research: 1 results,  Invited: 6 results)

  • [Journal Article] Clinical and Immunological Analyses of Ten Patients with MIRAGE Syndrome.2021

    • Author(s)
      Mitsui-Sekinaka K, Narumi S, Sekinaka Y, Uematsu K, Yoshida Y, Amano N, Shima H, Hasegawa T, Nonoyama S.
    • Journal Title

      J Clin Immunol.

      Volume: 41 Issue: 3 Pages: 709-711

    • DOI

      10.1007/s10875-020-00964-7

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] MIRAGE syndrome is a rare cause of 46,XY DSD born SGA without adrenal insufficiency.2018

    • Author(s)
      Shima H, Hayashi M, Tachibana T, Oshiro M, Amano N, Ishii T, Haruna H, Igarashi M, Kon M, Fukuzawa R, Tanaka Y, Fukami M, Hasegawa T, Narumi S.
    • Journal Title

      PLoS One.

      Volume: 13 Issue: 11 Pages: e0206184-e0206184

    • DOI

      10.1371/journal.pone.0206184

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] MIRAGE症候群2018

    • Author(s)
      鳴海覚志、長谷川奉延
    • Journal Title

      周産期医学

      Volume: 48 Pages: 1526-1530

    • Related Report
      2018 Research-status Report
  • [Journal Article] MIRAGE症候群 先天性副腎低形成症を主徴とする新たな遺伝子疾患2018

    • Author(s)
      鳴海覚志、長谷川奉延
    • Journal Title

      最新医学

      Volume: 73 Pages: 1115-1120

    • NAID

      40021652362

    • Related Report
      2018 Research-status Report
  • [Presentation] 副腎で輝く星・副腎に見える蜃気楼2021

    • Author(s)
      長谷川奉延
    • Organizer
      名古屋糖尿病・内分泌Online研究会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 小児期発症原発性副腎機能低下症の分子基盤2020

    • Author(s)
      長谷川奉延
    • Organizer
      第93回日本内分泌学会学術総会教育講演
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 生化学的評価で原因特定が困難な小児期発症原発性副腎皮質機能低下症における既知単一遺伝病の頻度および新たに疾患単位として確立したMIRAGE症候群2019

    • Author(s)
      長谷川奉延
    • Organizer
      第27回日本ステロイドホルモン学会学術集会シンポジウム
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Novel Genetic Mechanisms in Adrenal Disorders.2019

    • Author(s)
      長谷川奉延
    • Organizer
      6th Annual Endocrinology Debate and Global Exchange
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 副腎で輝く星・副腎に見える蜃気楼2019

    • Author(s)
      長谷川奉延
    • Organizer
      第6回PA・Aldosterone関連疾患研究会特別講演
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Cutting edge: 日本から発信する新しい疾患概念 MIRAGE症候群―新規疾患単位の確立とその後の“思いもよらない”展開―2018

    • Author(s)
      長谷川奉延
    • Organizer
      第28回臨床内分泌代謝Update
    • Related Report
      2018 Research-status Report
    • Invited

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Published: 2018-04-23   Modified: 2022-01-27  

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