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Revertant mosaicism in congenital ichthyoses

Research Project

Project/Area Number 17H06271
Research Category

Grant-in-Aid for Challenging Research (Pioneering)

Allocation TypeSingle-year Grants
Research Field Organ-based internal medicine and related fields
Research InstitutionHokkaido University

Principal Investigator

Shimizu Hiroshi  北海道大学, 医学研究院, 教授 (00146672)

Co-Investigator(Kenkyū-buntansha) 乃村 俊史  北海道大学, 大学病院, 講師 (50399911)
Project Period (FY) 2017-06-30 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥26,000,000 (Direct Cost: ¥20,000,000、Indirect Cost: ¥6,000,000)
Fiscal Year 2019: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Fiscal Year 2018: ¥10,400,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥2,400,000)
Fiscal Year 2017: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Keywords先天性魚鱗癬 / 魚鱗癬 / 組換え / revertant mosaicism / 相同組換え
Outline of Final Research Achievements

In this study, we demonstrated that homologous recombination underlies reversion of pathogenic mutations in ichthyosis with confetti. We also showed that loricrin keratoderma represents revertant mosaicism. Although the precise mechanisms underlying reversion of mutations remain unclear, we demonstrated that (1) mutant protein does not increase DNA double strand break (DSB), (2) mutant protein does not affect the pathway choice in the repair of DSB induced by X-ray irradiation, (3) mutant protein does not increase replication stress, and (4) mutant protein alters replication stress response.

Academic Significance and Societal Importance of the Research Achievements

遺伝性疾患は、極めて難治性で新規治療法の開発が強く希求されている。遺伝性角化症は稀な疾患ではあるが、変異タンパク質が相同組換えを誘発する機構、すなわち病因遺伝子変異が自然に消失するメカニズムを解明できれば、遺伝性疾患全般の治療に広く応用できる可能性がある。人為的に相同組換えを誘導することで病因変異を消失させることができれば、これまで有効な治療法が存在しなかった疾患に対する新規治療法の開発が期待できるはずである。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (12 results)

All 2020 2019 2018 2017

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (9 results) (of which Int'l Joint Research: 2 results,  Invited: 3 results)

  • [Journal Article] Recombination-induced revertant mosaicism in ichthyosis with confetti and loricrin keratoderma2020

    • Author(s)
      Toshifumi Nomura
    • Journal Title

      Journal of Dermatological Science

      Volume: 97 Issue: 2 Pages: 94-100

    • DOI

      10.1016/j.jdermsci.2019.12.013

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Somatic recombination underlies frequent revertant mosaicism in loricrin keratoderma2019

    • Author(s)
      Suzuki Shotaro、Nomura Toshifumi、Miyauchi Toshinari、Takeda Masae、Fujita Yasuyuki、Nishie Wataru、Akiyama Masashi、Ishida-Yamamoto Akemi、Shimizu Hiroshi
    • Journal Title

      Life Science Alliance

      Volume: 2 Issue: 1 Pages: e201800284-e201800284

    • DOI

      10.26508/lsa.201800284

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chromosomal inversions as a hidden disease-modifying factor for somatic recombination phenotypes.2018

    • Author(s)
      Nomura T, Suzuki S, Miyauchi T, Takeda M, Shinkuma S, Fujita Y, Nishie W, Akiyama M, Shimizu H
    • Journal Title

      JCI Insight

      Volume: 3 Issue: 6

    • DOI

      10.1172/jci.insight.97595

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 遺伝性角化症におけるrevertant mosaicism2019

    • Author(s)
      乃村俊史
    • Organizer
      第34回角化症研究会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Mitotic recombination underlies frequent revertant mosaicism in loricrin keratoderma2019

    • Author(s)
      乃村俊史,鈴木翔多朗,宮内俊成,竹田真依,藤田靖幸,西江 渉,秋山真志,山本明美,清水 宏
    • Organizer
      日本人類遺伝学会第64回大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 体細胞組換えによるrevertant mosaicismを認めたロリクリン角皮症の2家系2019

    • Author(s)
      乃村俊史,鈴木翔多朗,宮内俊成,竹田真依,藤田靖幸,西江 渉,秋山真志,山本明美,清水 宏
    • Organizer
      第83回日本皮膚科学会東京・東部合同学術大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Chromosomal inversions as a hidden disease-modifying factor for somatic recombination phenotypes2019

    • Author(s)
      Toshifumi Nomura
    • Organizer
      The 44th Annual Meeting of the Japanese Society for Investigative Dermatology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 皮膚バリア異常とアトピー性皮膚炎、魚鱗癬.2018

    • Author(s)
      乃村俊史
    • Organizer
      第82回日本皮膚科学会東部支部学術大会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Ichthyosis with confettiの一例2018

    • Author(s)
      乃村俊史、清水宏
    • Organizer
      第466回日本皮膚科学会大阪地方会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 診断に難渋した先天性魚鱗癬の1例2017

    • Author(s)
      乃村俊史, 鈴木翔多朗, 宮内俊成, 竹田真依, 藤田靖幸, 西江渉, 秋山真志, 清水宏
    • Organizer
      第32回角化症研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Chromosomal inversions as a hidden disease-modifying factor2017

    • Author(s)
      Nomura T, Suzuki S, Miyauchi T, Takeda M, Fujita Y, Nishie W, Akiyama M, Shimizu H
    • Organizer
      The 47th Annual European Society for Dermatological Research Meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 魚鱗癬と掌蹠角化症:症例から見えてきたこと2017

    • Author(s)
      乃村俊史
    • Organizer
      群馬皮膚科セミナー
    • Related Report
      2017 Annual Research Report
    • Invited

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Published: 2017-07-21   Modified: 2021-02-19  

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