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Elucidation of pathogenesis of mevalonate kinase deficiency with clinical samples, iPS cells, and mouse model

Research Project

Project/Area Number 15K19610
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Pediatrics
Research InstitutionKyoto University

Principal Investigator

Tanaka Takayuki  京都大学, 医学研究科, 医員 (20625678)

Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsiPS細胞 / 自己炎症性疾患 / サイトカイン / サイトカイン産生 / マウスモデル / iPS細胞由来単球 / 病態再現
Outline of Final Research Achievements

We produced CD14-positive blood cells through iPS cells derived 3 MKD patients and 2 healthy controls. The MK activity of patient-derived blood cells was potently reduced and below 2% of healthy controls, so the phenotype of the peripheral blood cells was reproduced in iPS cell-derived blood cells. Next, we compared IL-1beta secretion from iPS-derived blood cells, but found no difference between parient-derived and control cells.
We developed genetically-engineered mouse that express heterozygous mutant MVK gene. Then we bred them and obtained homozygous mutant mouse.
We identified 10 Japanese MKD patients in total, including newly-diagnosed patients during the research period. We are preparing to submit a paper regarding the clinical and laboratory information.

Report

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

    (3 results)

All 2016 2015

All Presentation (3 results)

  • [Presentation] 本邦でのメバロン酸キナーゼ欠損症のまとめ2016

    • Author(s)
      田中孝之 吉岡耕平 酒井秀政 西小森隆太 日衞嶋栄太郎 阿部純也 小原收 河合朋樹 八角高裕 平家俊男
    • Organizer
      第60回 日本リウマチ学会 総会・学術集会
    • Place of Presentation
      パシフィコ横浜、横浜市
    • Year and Date
      2016-04-21
    • Related Report
      2016 Annual Research Report
  • [Presentation] 本邦でのメバロン酸キナーゼ欠損症のまとめ2015

    • Author(s)
      田中孝之 吉岡耕平 酒井秀政 西小森隆太 日衛嶋栄太郎 井澤和司 阿部純也 小原収 河合朋樹 八角高裕 平家俊男
    • Organizer
      第25回日本小児リウマチ学会学術集会
    • Place of Presentation
      金沢歌劇座、金沢市
    • Year and Date
      2015-10-10
    • Related Report
      2015 Research-status Report
  • [Presentation] 本邦でのメバロン酸キナーゼ欠損症のまとめ2015

    • Author(s)
      田中孝之 吉岡耕平 酒井秀政 西小森隆太 日衛嶋栄太郎 井澤和司 阿部純也 小原収 河合朋樹 八角高裕 平家俊男
    • Organizer
      第39回日本小児皮膚科学会学術大会
    • Place of Presentation
      かごしま県民交流センター、鹿児島市
    • Year and Date
      2015-07-18
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2018-03-22  

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