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Age-related and mutation-independent proteomic changes in dystrophic mouse muscle

Research Project

Project/Area Number 18K07544
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52020:Neurology-related
Research InstitutionNational Center of Neurology and Psychiatry

Principal Investigator

Aoki Yoshitsugu  国立研究開発法人国立精神・神経医療研究センター, 神経研究所 遺伝子疾患治療研究部, 部長 (80534172)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
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: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsデュシェンヌ型筋ジストロフィー / サルコペニア / 筋萎縮 / 速筋型タイプII筋線維 / 超高感度定量質量分析 / 加齢 / 骨格筋 / 定量質量分析 / インタラクトミクス / マウス / プロテオミクス解析 / 筋ジストロフィー / プロテオミクス / 老化 / 神経内科
Outline of Final Research Achievements

Duchenne muscular dystrophy (DMD) is a severe muscle-wasting disease characterised by loss of ambulation and cardiorespiratory problems. At this moment, many aspects of the pathology and disease progression over time are still unclear. Here, we have utilised high-resolution isoelectric focusing liquid chromatography-mass spectrometry to investigate differential protein expression in the tibialis anterior (TA) of mdx, mdx52 and wild-type controls (C57BL/6) at 8, 16 and 80 weeks of age. This technique has provided improved resolution of the proteome, whereby 4974 proteins were detected in all samples. Only slight differences in protein expression were observed between mdx and mdx52. This analysis showed apparent differences between the control and two dystrophic mice with 2148 proteins differentially expressed (t-Test, P=0.01). Additionally, protein expression changed significantly with ageing for both groups.

Academic Significance and Societal Importance of the Research Achievements

本研究成果は筋萎縮の複雑な分子病態の解明に基づき、筋ジストロフィーおよび社会的課題であるサルコペニアの克服につながる。

Report

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

    (36 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (4 results) Journal Article (12 results) (of which Int'l Joint Research: 9 results,  Peer Reviewed: 12 results,  Open Access: 11 results) Presentation (10 results) (of which Int'l Joint Research: 3 results,  Invited: 9 results) Book (7 results) Patent(Industrial Property Rights) (3 results) (of which Overseas: 1 results)

  • [Int'l Joint Research] オックスフォード大学(英国)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] カロリンスカ研究所(スウェーデン)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] オックスフォード大学(英国)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] カロリンスカ研究所(スウェーデン)

    • Related Report
      2018 Research-status Report
  • [Journal Article] Immortalized Canine Dystrophic Myoblast Cell Lines for Development of Peptide-Conjugated Splice-Switching Oligonucleotides2021

    • Author(s)
      Tone Yuichiro、Mamchaoui Kamel、Tsoumpra Maria K.、Hashimoto Yasumasa、Terada Reiko、Maruyama Rika、Gait Michael J.、Arzumanov Andrey A.、McClorey Graham、Imamura Michihiro、Takeda Shin'ichi、Yokota Toshifumi、Wood Matthew J.A.、Mouly Vincent、Aoki Yoshitsugu
    • Journal Title

      Nucleic Acid Therapeutics

      Volume: 31 Issue: 2 Pages: 172-181

    • DOI

      10.1089/nat.2020.0907

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Mutation-independent Proteomic Signatures of Pathological Progression in Murine Models of Duchenne Muscular Dystrophy2020

    • Author(s)
      van Westering Tirsa L.E.、Johansson Henrik J.、Hanson Britt、Coenen-Stass Anna M.L.、Lomonosova Yulia、Tanihata Jun、Motohashi Norio、Yokota Toshifumi、Takeda Shin'ichi、Lehti? Janne、Wood Matthew J.A.、EL Andaloussi Samir、Aoki Yoshitsugu、Roberts Thomas C.
    • Journal Title

      Molecular & Cellular Proteomics

      Volume: 19 Issue: 12 Pages: 2047-2068

    • DOI

      10.1074/mcp.ra120.002345

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Novel EGFP reporter cell and mouse models for sensitive imaging and quantification of exon skipping2020

    • Author(s)
      Hara Yuko、Mizobe Yoshitaka、Inoue Yukiko U.、Hashimoto Yasumasa、Motohashi Norio、Masaki Yoshiaki、Seio Kohji、Takeda Shin’ichi、Nagata Tetsuya、Wood Matthew J. A.、Inoue Takayoshi、Aoki Yoshitsugu
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 10110-10110

    • DOI

      10.1038/s41598-020-67077-4

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Severe cardiac involvement with preserved truncated dystrophin expression in Becker muscular dystrophy by +1G>A DMD splice-site mutation: a case report2020

    • Author(s)
      Komaki Ryouhei、Hashimoto Yasumasa、Mori-Yoshimura Madoka、Oya Yasushi、Takizawa Hotake、Minami Narihiro、Nishino Ichizo、Aoki Yoshitsugu、Takahashi Yuji
    • Journal Title

      Journal of Human Genetics

      Volume: 65 Issue: 10 Pages: 903-909

    • DOI

      10.1038/s10038-020-0788-9

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dystrobrevin alpha gene is a direct target of the vitamin D receptor in muscle2020

    • Author(s)
      Tsoumpra Maria K、Sawatsubashi Shun、Imamura Michihiro、Fukumoto Seiji、Takeda Shin’ichi、Matsumoto Toshio、Aoki Yoshitsugu
    • Journal Title

      Journal of Molecular Endocrinology

      Volume: 64 Issue: 3 Pages: 195-208

    • DOI

      10.1530/jme-19-0229

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Publisher Correction: Modelling Duchenne muscular dystrophy in MYOD1-converted urine-derived cells treated with 3-deazaneplanocin A hydrochloride2020

    • Author(s)
      Takizawa Hotake、Hara Yuko、Mizobe Yoshitaka、Ohno Taisuke、Suzuki Sadafumi、Inoue Ken、Takeshita Eri、Shimizu-Motohashi Yuko、Ishiyama Akihiko、Hoshino Mikio、Komaki Hirofumi、Takeda Shin’ichi、Aoki Yoshitsugu
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 1-11

    • DOI

      10.1038/s41598-020-59351-2

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Modelling Duchenne muscular dystrophy in MYOD1-converted urine-derived cells treated with 3-deazaneplanocin A hydrochloride2019

    • Author(s)
      Takizawa Hotake、Hara Yuko、Mizobe Yoshitaka、Ohno Taisuke、Suzuki Sadafumi、Inoue Ken、Takeshita Eri、Shimizu-Motohashi Yuko、Ishiyama Akihiko、Hoshino Mikio、Komaki Hirofumi、Takeda Shin’ichi、Aoki Yoshitsugu
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 3807-3807

    • DOI

      10.1038/s41598-019-40421-z

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Peptide-conjugate antisense based splice-correction for Duchenne muscular dystrophy and other neuromuscular diseases2019

    • Author(s)
      Tsoumpra Maria K.、Fukumoto Seiji、Matsumoto Toshio、Takeda Shin'ichi、Wood Matthew J.A.、Aoki Yoshitsugu
    • Journal Title

      EBioMedicine

      Volume: 45 Pages: 630-645

    • DOI

      10.1016/j.ebiom.2019.06.036

    • NAID

      120006941112

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Potential Therapies Using Myogenic Stem Cells Combined with Bio-Engineering Approaches for Treatment of Muscular Dystrophies2019

    • Author(s)
      Motohashi Norio、Shimizu-Motohash Yuko、Roberts Thomas、Aoki Yoshitsugu
    • Journal Title

      Cells

      Volume: 8 Issue: 9 Pages: 1066-1066

    • DOI

      10.3390/cells8091066

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Application of Urine-Derived Stem Cells to Cellular Modeling in Neuromuscular and Neurodegenerative Diseases2019

    • Author(s)
      Sato Mitsuto、Takizawa Hotake、Nakamura Akinori、Turner Bradley J.、Shabanpoor Fazel、Aoki Yoshitsugu
    • Journal Title

      Frontiers in Molecular Neuroscience

      Volume: 12 Pages: 1-9

    • DOI

      10.3389/fnmol.2019.00297

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Autoimmune response and its long‐term consequences after exon‐skipping therapy in a Duchenne muscular dystrophy mouse model2019

    • Author(s)
      Nordin Joel Z、Aoki Yoshitsugu
    • Journal Title

      The Journal of Pathology

      Volume: 249 Issue: 3 Pages: 271-273

    • DOI

      10.1002/path.5327

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Restoring Dystrophin Expression in Duchenne Muscular Dystrophy: Current Status of Therapeutic Approaches2019

    • Author(s)
      Shimizu-Motohashi Yuko、Komaki Hirofumi、Motohashi Norio、Takeda Shin’ichi、Yokota Toshifumi、Aoki Yoshitsugu
    • Journal Title

      Journal of Personalized Medicine

      Volume: 9 Issue: 1 Pages: 1-1

    • DOI

      10.3390/jpm9010001

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] デュシェンヌ型筋ジストロフィーに対する創薬開発とアンチセンス核酸医薬2021

    • Author(s)
      青木吉嗣
    • Organizer
      第20回日本再生医療学会総会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] デュシェンヌ型筋ジストロフィーのエクソン・スキップ治療2020

    • Author(s)
      青木吉嗣
    • Organizer
      第38回日本神経治療学会学術集会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] デュシェンヌ型筋ジストロフィーのエクソン・スキップ治療2020

    • Author(s)
      青木吉嗣
    • Organizer
      第6回日本筋学会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] デュシェンヌ型筋ジストロフィーに対する核酸医薬品開発の最新知見2020

    • Author(s)
      青木吉嗣
    • Organizer
      第415回CBI学会講演会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 神経筋難病の遺伝子を標的にした治療法開発2019

    • Author(s)
      青木吉嗣
    • Organizer
      神経治療学会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] ジストロフィン欠損と加齢による骨格筋萎縮発症の分子機序解明2019

    • Author(s)
      青木吉嗣
    • Organizer
      東京農工大学―NCNP 第 5 回合同シンポジウム
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Dystrophin networks in the brain of mdx and mdx52 mice2019

    • Author(s)
      青木吉嗣
    • Organizer
      249th European Neuromuscular Centre International Workshop
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Advanced PPMO combinations drive multi-exon skipping and dystrophin expression in dystrophic dogs2019

    • Author(s)
      青木吉嗣
    • Organizer
      48th European Muscle Conference
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Targeting RNA to treat Duchenne muscular dystrophy2019

    • Author(s)
      青木吉嗣
    • Organizer
      CNMC International Conference
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Significance of animal experimentation to drug development for muscular dystrophy2018

    • Author(s)
      青木吉嗣
    • Organizer
      UCL London lecture
    • Related Report
      2018 Research-status Report
    • Invited
  • [Book] 実験医学2020年10月号2020

    • Author(s)
      青木吉嗣
    • Total Pages
      8
    • Publisher
      羊土社
    • ISBN
      9784758125369
    • Related Report
      2020 Annual Research Report
  • [Book] ダイレクトリプログラミング ~ 再生医療の新展開 ~2020

    • Author(s)
      青木吉嗣
    • Total Pages
      8
    • Publisher
      エヌ・ティー・エス
    • ISBN
      9784860436711
    • Related Report
      2020 Annual Research Report
  • [Book] MD Frontier 筋ジストロフィー診療の今を考える2020

    • Author(s)
      青木吉嗣
    • Total Pages
      8
    • Publisher
      メディカルレビュー社
    • ISBN
      9784779225598
    • Related Report
      2020 Annual Research Report
  • [Book] CLINICAL NEUROSCIENCE2020

    • Author(s)
      青木吉嗣
    • Total Pages
      6
    • Publisher
      中外医学社
    • Related Report
      2019 Research-status Report
  • [Book] PHARM TECH JAPAN2019

    • Author(s)
      青木吉嗣
    • Total Pages
      6
    • Publisher
      じほう
    • Related Report
      2019 Research-status Report
  • [Book] PrecisionMedicine2019

    • Author(s)
      青木吉嗣
    • Total Pages
      6
    • Publisher
      北隆館
    • Related Report
      2019 Research-status Report
  • [Book] アンチセンス医薬開発の最前線(2)神経・筋疾患に対するアンチセンス医薬品2019

    • Author(s)
      青木吉嗣
    • Total Pages
      6
    • Publisher
      医薬品医療機器レギュラトリーサイエンス財団
    • Related Report
      2019 Research-status Report
  • [Patent(Industrial Property Rights)] エクソン51のスキッピングを誘導するアンチセンス核酸2020

    • Inventor(s)
      青木吉嗣
    • Industrial Property Rights Holder
      青木吉嗣
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Related Report
      2019 Research-status Report
  • [Patent(Industrial Property Rights)] エクソン50のスキッピングを誘導するアンチセンス核酸2020

    • Inventor(s)
      青木吉嗣
    • Industrial Property Rights Holder
      青木吉嗣
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Related Report
      2019 Research-status Report
  • [Patent(Industrial Property Rights)] アンチセンス核酸(エクソン45)2020

    • Inventor(s)
      青木吉嗣
    • Industrial Property Rights Holder
      青木吉嗣
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Acquisition Date
      2020
    • Related Report
      2019 Research-status Report
    • Overseas

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

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