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An attempt to improve pathology of muscular dystrophy model rats by preventing cellular senescence.

Research Project

Project/Area Number 15K14883
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Integrative animal science
Research InstitutionThe University of Tokyo

Principal Investigator

Yamanouchi Keitaro  東京大学, 大学院農学生命科学研究科(農学部), 准教授 (70272440)

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)
Keywords筋ジストロフィー / 骨格筋 / 筋再生 / 細胞老化 / 筋衛星細胞 / 間葉系前駆細胞 / ゲノム編集
Outline of Final Research Achievements

We previously succeeded in generating rats having out-of-frame mutation in dystrophin gene by genome editing. The rats show very severe phenotype in their skeletal muscle, which is similar to that seen in Duchenne muscular dystrophy patients. Since the expression of p16, a senescent cell marker, was up-regulated in skeletal muscle of dystrophin-mutated rats, we hypothesized cellular senescence is involved in the progression of skeletal muscle pathology. As a result, we found that TGF-β expression is increased in the skeletal muscle of dystrophin-mutated rats, and thus increased TGF-β induces cellular senescence in satellite cells.

Report

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

    (9 results)

All 2017 2016 2015

All Presentation (9 results) (of which Int'l Joint Research: 1 results,  Invited: 4 results)

  • [Presentation] A novel rat model of muscular dystrophy and newly identified functional molecule in mesenchymal progenitor cells.2017

    • Author(s)
      Yamanouchi K
    • Organizer
      The 8th Joint Symposium of Veterinery research among Universities of Veterinary Medicine in East Asia
    • Place of Presentation
      Taichung, Taiwan
    • Year and Date
      2017-02-20
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 再生器官としての筋肉とその疾患2016

    • Author(s)
      山内啓太郎
    • Organizer
      日本チャールズリバー株式会社 教育講演
    • Place of Presentation
      日本チャールズリバー株式会社(茨城県つくば市)
    • Year and Date
      2016-09-09
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 哺乳類骨格筋の発達と再生に関する研究2016

    • Author(s)
      山内啓太郎
    • Organizer
      第159回日本獣医学会 学会賞記念講演
    • Place of Presentation
      日本大学(神奈川県藤沢市)
    • Year and Date
      2016-09-07
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] ジストロフィン遺伝子変異ラットの骨格筋病変に対する細胞老化の関与2016

    • Author(s)
      杉原英俊、寺本奈保美、中村克行、志賀崇徳、松脇貴志、山内啓太郎、西原真杉
    • Organizer
      第159回日本獣医学会
    • Place of Presentation
      日本大学(神奈川県藤沢市)
    • Year and Date
      2016-09-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] Pathological evaluation of rats carrying CRISPRE/Cas-9-mediated in-frame mutaion in dystrophin gene.2016

    • Author(s)
      Teramoto N, Sugihara H, Nakamura K, Shiga T, Tanihata J, Matsuwaki T, Yamanouchi K, Nishihara M
    • Organizer
      FASEB summer research conference "Skeletal Muscle Satellite Cells and Regeneration"
    • Place of Presentation
      Keystone, CO, USA
    • Year and Date
      2016-07-25
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ゲノム編集を用いた筋疾患モデルラットの作出とその病態解析2015

    • Author(s)
      山内啓太郎
    • Organizer
      第91回 実験動物コンファレンス
    • Place of Presentation
      日本獣医生命科学大学(東京・武蔵野市)
    • Year and Date
      2015-12-12
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] Dystrophin遺伝子にin frame変異をもつラットの表現型解析2015

    • Author(s)
      寺本奈保美、中村克行、杉原英俊、志賀崇徳、谷端淳、松脇貴志、山内啓太郎、西原真杉
    • Organizer
      第158回 日本獣医学会
    • Place of Presentation
      北里大学(青森・十和田市)
    • Year and Date
      2015-09-08
    • Related Report
      2015 Research-status Report
  • [Presentation] デュシェンヌ型筋ジストロフィーの病態悪化に細胞老化が関与する可能性2015

    • Author(s)
      杉原英俊、中村克行、寺本奈保美、志賀崇徳、松脇貴志、山内啓太郎、西原真杉
    • Organizer
      第1回 日本筋学会
    • Place of Presentation
      精神神経センター(東京・小平市)
    • Year and Date
      2015-08-08
    • Related Report
      2015 Research-status Report
  • [Presentation] Dystrophin遺伝子にin-frame変異をもつラットの表現型の解析2015

    • Author(s)
      寺本奈保美、中村克行、杉原英俊、志賀崇徳、谷端淳、松脇貴志、山内啓太郎、西原真杉
    • Organizer
      第1回 日本筋学会
    • Place of Presentation
      精神神経センター(東京・小平市)
    • Year and Date
      2015-08-08
    • Related Report
      2015 Research-status Report

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

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