• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Elucidation the pathomechanisms of conformational diseases through analyzing the model mice of sporadic inclusion myositis

Research Project

Project/Area Number 26860674
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Neurology
Research InstitutionKumamoto University

Principal Investigator

Tawara Akie  熊本大学, 医学部附属病院, 医員 (00726333)

Research Collaborator ANDO Yukio  
YAMASHITA Satoshi  
TAWARA Nozomu  
Doki Tsukasa  
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords孤発性封入体筋炎 / TDP-43 / LC-MS/MS / NT5C1A / 封入体筋炎 / プロテオミクス解析
Outline of Final Research Achievements

Sporadic inclusion body myositis (sIBM) demonstrates inflammatory findings and degenerative features. Recently, TAR DNA-binding protein of 43 kDa (TDP-43) has been reported to be accumulated within degenerative myofibers of sIBM. At this point, it remained unclear whether the sarcoplasmic accumulation of TDP-43 is a primary trigger of muscle degeneration. The aim of our study is to dissolve whether muscle-dominant overexpression of TDP-43 can primarily cause muscle degeneration. We generated mice with muscle-dominant TDP-43 expression, and analyzed the phenotypes using biochemical, histological, and proteomic techniques including laser microdissection with LC-MS/MS. TDP-43 transgenic mice showed increased levels of CK. Myopathology demonstrated vacuolar formation and aggregation of TDP-43. Proteomic analysis using aggregated materials in degenerative myofibers identified increased levels of chaperons recognizing misfiled proteins. TDP-43 expression indeed caused myofiber degeneration.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (9 results)

All 2015 2014

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (7 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Clinicopathological features of the first Asian family having vocal cord and pharyngeal weakness with distal myopathy due to a MATR3 mutation.2015

    • Author(s)
      Yamashita S, Mori A, Nishida Y, Kurisaki R, Tawara N, Nishikami T, Misumi Y, Ueyama H, Imamura S, Higuchi Y, Hashiguchi A, Higuchi I, Morishita S, Yoshimura J, Uchino M, Takashima H, Tsuji S, Ando Y.
    • Journal Title

      Neuropathol Appl Neurobiol

      Volume: 41 Issue: 3 Pages: 391-398

    • DOI

      10.1111/nan.12179

    • Related Report
      2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Clinical features of Japanese patients with inclusion body myositis.2014

    • Author(s)
      Hori H, Yamashita S, Tawara N, Hirahara T, Kawakami K, Nishikami T, Maeda Y, Ando Y
    • Journal Title

      Journal of the Neurological Sciences.

      Volume: Volume 346, Issues 1-2 Pages: 133-137

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] Analysis of the pathogenesis of vocal cord and pharyngeal weakness with distal myopathy2015

    • Author(s)
      S. Yamashita; T. Nishikami; N. Tawara; T. Doki; Y. Nakajo; Y. Matsuo; Y. Yonemochi; M. Nagai; Y. Maeda; Y. Ando
    • Organizer
      20th International Congress of The World Muscle Society.
    • Place of Presentation
      Brighton, UK
    • Year and Date
      2015-09-30
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] A single center analysis of the clinicopathological findings of anti-cytosolic 5′-nucleotidase 1a antibody-positive sporadic inclusion body myositis2015

    • Author(s)
      N. Tawara; S. Yamashita; T. Nishikami; Y. Nakajou; T. Doki; Y. Matsuo; Y. Yonemochi; Y. Maeda; Y. Ando
    • Organizer
      20th International Congress of The World Muscle Society.
    • Place of Presentation
      Brighton, UK
    • Year and Date
      2015-09-30
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 筋特異的TDP-43トランスジェニックマウスの変性筋内蛋白の網羅的解析2015

    • Author(s)
      山元 康寛、山下 賢、川上 賢祐、俵 望、田崎 雅義、西上 朋、道鬼 つかさ、松尾 圭将、安東 由喜雄
    • Organizer
      第56回日本神経学会学術大会
    • Place of Presentation
      新潟
    • Year and Date
      2015-05-20 – 2015-05-23
    • Related Report
      2014 Research-status Report
  • [Presentation] Analyses of the pathogenesis in muscle-specific wild-type TDP-43 transgenic mice.2014

    • Author(s)
      Yamashita S, Kawakami K, Nishikami T, Tawara N, Y. Maeda Y. Ando Y.
    • Organizer
      19th International Congress of The World Muscle Society.
    • Place of Presentation
      ドイツ、ベルリン
    • Year and Date
      2014-10-08 – 2014-10-11
    • Related Report
      2014 Research-status Report
  • [Presentation] Cytoplasmic 5'-nucleotidase 1A are aggregated in type 2 fiber in sporadic inclusion body myositis.2014

    • Author(s)
      Tawara N, Yamashita N, Nishikami T, Kawakami K, Tawara A,Hori H, Hirahara T, Maeda Y, Ando Y.
    • Organizer
      19th International Congress of The World Muscle Society.
    • Place of Presentation
      ドイツ、ベルリン
    • Year and Date
      2014-10-08 – 2014-10-11
    • Related Report
      2014 Research-status Report
  • [Presentation] The first Asian family having vocal cord and pharyngeal weakness with distal myopathy due to a MATR3 mutation.2014

    • Author(s)
      Nishikami T, Yamashita S, Tawara N, Mori A, Hori H, Hirahara T, Maeda Y, Ando Y.
    • Organizer
      19th International Congress of The World Muscle Society.
    • Place of Presentation
      ドイツ、ベルリン
    • Year and Date
      2014-10-08 – 2014-10-11
    • Related Report
      2014 Research-status Report
  • [Presentation] 筋特異的なTDP-43発現によるIBMモデルマウス作製と病態解析2014

    • Author(s)
      山下賢、川上賢祐、西上朋、俵望、安東由喜雄
    • Organizer
      第55回日本神経学会学術大会
    • Place of Presentation
      福岡
    • Year and Date
      2014-05-21 – 2014-05-24
    • Related Report
      2014 Research-status Report

URL: 

Published: 2014-04-04   Modified: 2018-03-22  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi