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Molecular pathogenesis of myotonic dystrophy in the central nervous system

Research Project

Project/Area Number 23591258
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurology
Research InstitutionHyogo Medical University

Principal Investigator

TAKASHI Kimura  兵庫医科大学, 医学部, 講師 (20441264)

Co-Investigator(Kenkyū-buntansha) YOSHIKAWA Hiroo  兵庫医科大学, 教授 (90273680)
KUBO Shuji  兵庫医科大学, 准教授 (10441320)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2012: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2011: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Keywords筋強直性ジストロフィー / 中枢神経症状 / スプライシング異常 / MBNL1/2 / 国際情報交換 / 米国、フロリダ / 米国、フロリダ大学 / 国際情報交流
Research Abstract

We showed that nuclear sequestration of alternative splicing factors, muscleblind-like 1 (MBNL1) and MBNL2 explains splicing defects observed in human myotonic dystrophy type 1 (DM1) brain and the contribution of MBNL2 is greater than that of MBNL1. We found similar splicing defects in frontal cortex, temporal cortex, and hippocampus, but not in cerebellum from DM1 patients. It is probable that the shortest CTG repeat expansion could contribute to the lack of splicing defects in DM1 cerebellum. Also, the less expression of DMPK protein might be related with the fact that pathological abnormalities were not found in the DM1 cerebellum.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (21 results)

All 2013 2012 2011 Other

All Journal Article (4 results) (of which Peer Reviewed: 4 results) Presentation (17 results)

  • [Journal Article] Muscleblind-like 2-Mediated Alternative Splicing in the Developing Brain and Dysregulation in Myotonic Dystrophy2012

    • Author(s)
      Charizanis K, Lee KY, Batra R, Goodwin M, Zhang C, Yuan Y, Shiue L, Cline M, Scotti MM, Xia G, Kumar A, Ashizawa T, Clark HB, Kimura T, Takahashi MP, Fujimura H, Jinnai K, Yoshikawa H, Gomes-Pereira M, Gourdon G, Sakai N, Nishino S, Foster TC, Ares M, Jr., Darnell RB, Swanson MS
    • Journal Title

      Neuron

      Volume: 75(3) Pages: 437-50

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] T. Muscleblind-like 1 knockout mice reveal novel splicing defects in the myotonic dystrophy brain2012

    • Author(s)
      Suenaga K, Lee KY, Nakamori M, Tatsumi Y, Takahashi MP, Fujimura H, Jinnai K, Yoshikawa H, Du H, Ares M, Jr., Swanson MS, Kimura
    • Journal Title

      PLoS One

      Volume: 7(3)

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Muscleblind-like 2 mediated alternative splicing in the developing brain and dysregulation in myotonic dystrophy.2012

    • Author(s)
      Charizanis K, Lee K-Y, Batra R, 中略 Kimura T, Takahashi MP, Fujimura H, Jinnai K, Yoshikawa H, Gomes-Pereira M, Gourdon G, Sakai N, Nishino S, Ares Jr M, Darnell RB, Swanson M.
    • Journal Title

      Neuron

      Volume: 75 Issue: 3 Pages: 467-450

    • DOI

      10.1016/j.neuron.2012.05.029

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Muscleblind-like 1 Knockout Mice Reveal Novel Splicing Defects in the Myotonic Dystrophy Brain2012

    • Author(s)
      Suenaga K, Lee KY, Nakamori M, Tatsumi Y, Takahashi MP, Fujimura H, Jinnai K, Yoshikawa H, Du H, Ares M Jr, Swanson MS, Kimura T
    • Journal Title

      PLoS One

      Volume: 7(3) Issue: 3 Pages: e33218-e33218

    • DOI

      10.1371/journal.pone.0033218

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] Altered Splicing of Cardiac Sodium Channel Might Be Responsible for Cardiac Conduction Defects in Myotonic Dystrophy2013

    • Author(s)
      Yosuke KOKUNAI, Hideki ITOH, Yoshihiro KINO, Moyi LI, Masayuki NAKAMORI, Takashi KIMURA, Tsuyoshi MATSUMURA, Harutoshi, FUJIMURA, Nobuyuki NUKINA, Hideki MOCHIZUKI, Saburo SAKODA, Minoru HORIE, Shouichi ICHIURA, Keiji IMOTO, Maurice SWANSON, Nicolas CHARLET BERGUERAND, Masanori TAKAHASHI
    • Organizer
      9th International Myotonic Dystrophy Consortium Meeting
    • Place of Presentation
      San Sebastian, Spain
    • Year and Date
      2013-10-17
    • Related Report
      2013 Final Research Report
  • [Presentation] he distribution of splicing defects in the Myotonic Dystrophy type 1 brain2013

    • Author(s)
      Takashi KIMURA, Koichi SUENAGA, Masayuki NAKAMORI, Tsuyoshi MATSUMURA, Masanori TAKAHASHI, Harutoshi FUJIMURA, Kenji JINNAI, Hiroo YOSHIKAWA. T
    • Organizer
      9th International Myotonic Dystrophy Consortium Meeting
    • Place of Presentation
      San Sebastian, Spain
    • Year and Date
      2013-10-17
    • Related Report
      2013 Final Research Report
  • [Presentation] 筋強直性ジストロフィー症における中枢神経スプライシング異常の局在性の検討2013

    • Author(s)
      末永浩一、木村卓、中森雅之、高橋正紀、松村剛、藤村晴俊、陣内研二、芳川浩男
    • Organizer
      第54回日本神経学会学術大会
    • Place of Presentation
      東京
    • Year and Date
      2013-05-29
    • Related Report
      2013 Final Research Report 2012 Research-status Report
  • [Presentation] 筋強直性ジストロフィー症における中枢神経スプラシング異常およびその分子機序の解明2012

    • Author(s)
      末永浩一、木村卓、Kuang-Yung Lee、中森雅之、高橋正紀、藤村晴俊、陣内研二、久保秀司、玉置(橋本)知子、Manuel Ares Jr.、Maurice S. Swanson、芳川浩男
    • Organizer
      第53回日本神経学会学術大会
    • Place of Presentation
      東京
    • Year and Date
      2012-05-25
    • Related Report
      2013 Final Research Report
  • [Presentation] 筋強直性ジストロフィー症における中枢神経スプライシング異常およびその分子機序の解明2012

    • Author(s)
      末永浩一,木村卓,Lee K-Y ,中森雅之,高橋正紀,藤村晴俊,陣内研二,久保秀司,玉置(橋本)知子,Manuel A, Maurice S,芳川浩男
    • Organizer
      第53回日本神経学会学術大会
    • Place of Presentation
      東京
    • Related Report
      2012 Research-status Report
  • [Presentation] Muscleblind-like 2 knockout mice : a model for splicing alterations and neurological changes in the DM brain2011

    • Author(s)
      Charizanis K, Lee K-Y, Scotti MM, Xia G, Shiue L, Cline MS, Ares M Jr, Kimura T, Takahashi MP, Fujimura H, Jinnai K, Yoshikawa H, Swanson MS
    • Organizer
      8th International Myotonic Dystrophy Consortium Meeting
    • Place of Presentation
      Clearwater, USA
    • Year and Date
      2011-12-02
    • Related Report
      2013 Final Research Report
  • [Presentation] Muscleblind-like 1 Knockout Mice Reveal Novel Splicing Defects in the Myotonic Dystrophy Brain2011

    • Author(s)
      Kimura T, Lee K-Y, Suenaga K, Nakamori M, Tatsumi Y, Takahashi MP, Fujimura H, Jinnai K, Yoshikawa H, Du H, Ares M Jr., Swanson MS
    • Organizer
      8th International Myotonic Dystrophy Consortium Meeting
    • Place of Presentation
      Clearwater, USA
    • Year and Date
      2011-12-02
    • Related Report
      2013 Final Research Report
  • [Presentation] Altered splicing of cardiac sodium channel in heart muscles of myotonic dystrophy type 12011

    • Author(s)
      Kokunai Y, Kino Y, Moyi L, Itoh H, Nakamori M, Kimura T, Matsumura T, Fujimura H, Nukina N, Sakoda S, Horie M, Imoto K, Ishiura S, Swanson MS, Takahashi MP
    • Organizer
      8th International Myotonic Dystrophy Consortium Meeting
    • Place of Presentation
      Clearwater, USA
    • Year and Date
      2011-12-01
    • Related Report
      2013 Final Research Report
  • [Presentation] 筋強直性ジストロフィー症における中枢神経スプラシング異常およびその分子機序の解明2011

    • Author(s)
      末永浩一、木村卓、Kuang-Yung Lee、中森雅之、高橋正紀、松村到、藤村晴俊、陣内研二、久保秀司、玉置(橋本)知子、Manuel Ares Jr., Maurice S. Swanson,芳川浩男
    • Organizer
      第52回日本神経学会学術大会
    • Place of Presentation
      名古屋
    • Year and Date
      2011-05-19
    • Related Report
      2013 Final Research Report
  • [Presentation] 筋強直性ジストロフィー症におけるスプライシング異常およびその分子機序の解明2011

    • Author(s)
      末永浩一,木村卓,Lee K,中森雅之,高橋正紀,松村剛,藤村晴俊,陣内研二,久保秀司,玉置(橋本)知子,Ares M, Swanson MS, 芳川浩男
    • Organizer
      第52回日本神経学会学術大会
    • Place of Presentation
      名古屋
    • Related Report
      2011 Research-status Report
  • [Presentation] Muscleblind-like 2 knockout mice: a model for splicing alterations and neurological changes in the DM brain.2011

    • Author(s)
      Charizanis K, Lee K-Y, Scotti MM, Xia G, Shiue L, Cline MS, Ares M, Jr., Kimura T, Takahashi MP, Fujimura H, Jinnai K, Yoshikawa H, Swanson MS.
    • Organizer
      8th international myotonic dystrophy consortium meeting (IDMC-8)
    • Place of Presentation
      米国、クリアウォーター
    • Related Report
      2011 Research-status Report
  • [Presentation] Muscleblind-like 1 Knockout Mice Reveal Novel Splicing Defects in the Myotonic Dystrophy Brain.2011

    • Author(s)
      Kimura T, Lee K-Y, Suenaga K, Nakamori M, Tatsumi Y, Takahashi MP, Fujimura H, Jinnai K, Yoshikawa H, Du H, Ares M, Jr., Swanson MS.
    • Organizer
      8th international myotonic dystrophy consortium meeting (IDMC-8)
    • Place of Presentation
      米国、クリアウォーター
    • Related Report
      2011 Research-status Report
  • [Presentation] Altered splicing of cardiac sodium channel in heart muscles of myotonic dystrophy type 12011

    • Author(s)
      Kokunai Y, Kino Y, Moyi L, Itoh H, Nakamori M, Kimura T, Matsumura T, Fujimura H, Nukina N, Sakoda S, Horie M, Imoto K, Ishiura S, Swanson MS, Takahashi MP.
    • Organizer
      8th international myotonic dystrophy consortium meeting (IDMC-8)
    • Place of Presentation
      米国、クリアウォーター
    • Related Report
      2011 Research-status Report
  • [Presentation] 筋強直性ジストロフィー心筋におけるNaチャネルのスプライシング異常.2011

    • Author(s)
      穀内洋介, 中森雅之, 木村卓, 松村剛, 藤村晴俊, 佐古田三郎, 高橋正紀
    • Organizer
      第52回日本神経学会学術大会
    • Place of Presentation
      名古屋
    • Related Report
      2011 Research-status Report
  • [Presentation] Altered Splicing of Cardiac Sodium Channel Might Be Responsible for Cardiac Conduction Defects in Myotonic Dystrophy.

    • Author(s)
      Yosuke KOKUNAI, Hideki ITOH, Yoshihiro KINO, Moyi LI, Masayuki NAKAMORI, Takashi KIMURA, Tsuyoshi MATSUMURA, Harutoshi, FUJIMURA, Nobuyuki NUKINA, Hideki MOCHIZUKI, Saburo SAKODA, Minoru HORIE, Shouichi ICHIURA, Keiji IMOTO, Maurice SWANSON, Nicolas CHARLET BERGUERAND, Masanori TAKAHASHI.
    • Organizer
      9th International Myotonic Dystrophy Consortium Meeting
    • Place of Presentation
      San Sebastian, Spain
    • Related Report
      2013 Annual Research Report
  • [Presentation] The distribution of splicing defects in the Myotonic Dystrophy type 1 brain.

    • Author(s)
      Takashi KIMURA, Koichi SUENAGA, Masayuki NAKAMORI, Tsuyoshi MATSUMURA, Masanori TAKAHASHI, Harutoshi FUJIMURA, Kenji JINNAI, Hiroo YOSHIKAWA.
    • Organizer
      9th International Myotonic Dystrophy Consortium Meeting
    • Place of Presentation
      San Sebastian, Spain
    • Related Report
      2013 Annual Research Report
  • [Presentation] 筋強直性ジストロフィー症における中枢神経スプライシング異常の局在性の検討.

    • Author(s)
      末永浩一、木村 卓、中森雅之、高橋正紀、松村剛、藤村晴俊、陣内研二、芳川浩男.
    • Organizer
      第54回日本神経学会学術大会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report

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Published: 2011-08-05   Modified: 2019-07-29  

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