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メダカを用いた筋原線維性ミオパチーの病原・病態解明

Research Project

Project/Area Number 20659142
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Neurology
Research InstitutionNational Center of Neurology and Psychiatry

Principal Investigator

林 由起子  National Center of Neurology and Psychiatry, 神経研究所疾病研究第一部, 室長 (50238135)

Co-Investigator(Kenkyū-buntansha) 三橋 弘明  国立精神・神経センター, 神経研究所疾病研究第一部, 流動研究員 (20466220)
朴 英恩  国立精神・神経センター, 神経研究所疾病研究第一部, 流動研究員 (50466223)
Project Period (FY) 2008 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2009: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2008: ¥2,100,000 (Direct Cost: ¥2,100,000)
Keywords臨床神経分子遺伝学
Research Abstract

筋原線維性ミオパチー(Myofibrillar myopathy ; MFM)は、筋原線維配列の強い乱れを主な病理学的特徴とする筋疾患群で、Z線関連タンパク質の異常によるものと考えられているが、その約80%は原因不明である。本研究ではメダカを疾患モデル動物として、我々の見いだしたMFM関連遺伝子変異の導入個体を作製し、病態との関連を明らかにすることを目的とした。
メダカはすでにその全ゲノムが解読されているが、個々の遺伝子についてのmRNAの配列や発現は哺乳類と異なるものも多く、情報収集やコンストラクトの作製に時間を有する場合も多かった。現在、我々の見いだした新規のMFM原因候補遺伝子について野生型と変異型のコンストラクトを作製するとともに、保存されてない遺伝子に関してはヒト遺伝子のコンストラクトを効率よく発現させるベクターを複数検討中である。また骨格筋あるいは遅筋特異的にGFPやDs-redを発現するメダカを用いて、メダカにおける骨格筋の走行やその特徴を明らかにした。
一方、フィラミンC遺伝子変異メダカに関しては、ホモ接合体が孵化前後で死亡すること、心筋及び骨格筋に強い異常が認められることを形態的、病理学的に明らかにした。特に電子顕微鏡的観察により、骨格筋における筋原線維の走行異常が明らかであり、フィラミンCの筋原線維構築における重要性を明らかにした。現在ヘテロ接合体について経時的な筋線維変化を検討中であるが、週齢を経るにつれ、ヒトフィラミンC遺伝子変異例における筋病理変化と非常に良く似た筋原線維の構築異常が見いだされている。現在、メダカにおける各種抗体の有用性を検討しつつ、Z線構築タンパク質の変化や凝集について具体的なデータを集積している。

Report

(2 results)
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (32 results)

All 2010 2009 2008 Other

All Journal Article (9 results) (of which Peer Reviewed: 7 results) Presentation (20 results) Book (2 results) Remarks (1 results)

  • [Journal Article] Congenital myotonic dystrophy can show congenital fiber type disproportion pathology2010

    • Author(s)
      Tominaga K, Hayashi YK, 他
    • Journal Title

      Acta Neuropathol 119

      Pages: 481-486

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Defective myotilin homodimerization caused by a novel mutation in MYOT exon 9 in the first Japanese limb girdle muscular dystrophy 1A patient2009

    • Author(s)
      Shalaby S, Hayashi YK, 他
    • Journal Title

      J Neuropathol Exp Neurol 68

      Pages: 701-707

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Autophagic degradation of nuclear components in mammalian cells2009

    • Author(s)
      Park EU, Hayashi YK, 他
    • Journal Title

      Autophagy 5

      Pages: 795-804

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Human PTRF mutations cause secondary deficiency of caveolins resulting in muscular dystrophy with generalized lipodystrophy2009

    • Author(s)
      Hayashi YK, Matsuda C, 他
    • Journal Title

      J Clin Invest 119

      Pages: 2623-2633

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A novel POMT2 mutation causes mild congenital muscular dystrophy with normal brain MRI2009

    • Author(s)
      Murakami T, Hayashi YK, 他
    • Journal Title

      Brain Dev 31

      Pages: 465-468

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Emery-Dreifuss 型筋ジストロフィー2009

    • Author(s)
      林由起子
    • Journal Title

      小児内科増刊号(小児疾患診療のための病態生理) 41

      Pages: 887-889

    • Related Report
      2009 Annual Research Report
  • [Journal Article] Emery-Dreifuss 型筋ジストロフィーと類縁疾患の筋病理2009

    • Author(s)
      林由起子
    • Journal Title

      神経内科 特集 筋病理-最近の進歩- 71

      Pages: 354-359

    • Related Report
      2009 Annual Research Report
  • [Journal Article] Novel FHL1 mutations in fatal and benign reducing body myopathy2009

    • Author(s)
      Shalaby S, 他
    • Journal Title

      Neurology 72

      Pages: 375-376

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Defective myotilin homopdimerization caused by a novel mutation in MYOT Exon 9 in the first Japanese LGMD1A.2008

    • Author(s)
      Shalaby S, 他
    • Journal Title

      Neuromuscul Disord 18

      Pages: 959-961

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] A Novel Muscular Dystrophy Associated with Secondary Deficiency of Caveolin2010

    • Author(s)
      林由起子
    • Organizer
      The 9th Annual Asian and Oceanian Myology Center Scientific Meeting
    • Place of Presentation
      Millennium Seoul Hilton, Seoul, Korea
    • Year and Date
      2010-03-25
    • Related Report
      2009 Annual Research Report
  • [Presentation] 肢帯型筋ジストロフィー1A型患者に見出された myotilin のホモダイマー形成異常2009

    • Author(s)
      三橋弘明, Shalaby S, 松田知栄, 南成祐, 他
    • Organizer
      第82回日本生化学会大会
    • Place of Presentation
      神戸国際会議場, 神戸
    • Year and Date
      2009-10-24
    • Related Report
      2009 Annual Research Report
  • [Presentation] Autophagic degradation of nuclear components in mammalian cells2009

    • Author(s)
      Hayashi YK, Park YE, Bonne G, Arimura T, 他
    • Organizer
      The 5th International Symposium on Autophagy
    • Place of Presentation
      Ots Prince Hotel, Ots, Japan
    • Year and Date
      2009-09-28
    • Related Report
      2009 Annual Research Report
  • [Presentation] 二次性カベオリン欠損症の新規原因遺伝子同定とその臨床病態についての検討2009

    • Author(s)
      林由起子, 菅野尚, 萩野谷和裕, 福興なおみ, 他
    • Organizer
      日本人類遺伝学会第54回大会
    • Place of Presentation
      グランドホテル高輪, 東京
    • Year and Date
      2009-09-26
    • Related Report
      2009 Annual Research Report
  • [Presentation] New variant of myofibrillar myopathy with CNS involvement2009

    • Author(s)
      Shalaby S, Hayashi YK, Mitsuhashi H, Goto K, 他
    • Organizer
      14th International Congress of the World Muscle Society
    • Place of Presentation
      UNI-MAIL, Geneva, Switzerland
    • Year and Date
      2009-09-11
    • Related Report
      2009 Annual Research Report
  • [Presentation] Congenital myotonic dystrophy in patients diagnosed as congenital fiber type disproportion2009

    • Author(s)
      Tominaga K, Hayashi YK, Goto K, Minami N, 他
    • Organizer
      14th International Congress of the World Muscle Society
    • Place of Presentation
      UNI-MAIL, Geneva, Switzerland
    • Year and Date
      2009-09-11
    • Related Report
      2009 Annual Research Report
  • [Presentation] Inflammatory myopathy in early childhood is frequently associated with LMNA mutatios2009

    • Author(s)
      Komaki H, Hayashi YK, Kato M, Sakuma H, 他
    • Organizer
      14th International Congress of the World Muscle Society
    • Place of Presentation
      UNI-MAIL, Geneva, Switzerland
    • Year and Date
      2009-09-11
    • Related Report
      2009 Annual Research Report
  • [Presentation] Autophagic degradation of nuclear component in nuclear envelopathy2009

    • Author(s)
      Park YE, Hayashi YK, Bonne G, Arimura T, 他
    • Organizer
      14th International Congress of the World Muscle Society
    • Place of Presentation
      UNI-MAIL, Geneva, Switzerland
    • Year and Date
      2009-09-11
    • Related Report
      2009 Annual Research Report
  • [Presentation] A new antibody specifically recognizes muscles from laminopathy patients2009

    • Author(s)
      Mitsuhashi H, Hayashi YK, Noguchi S, Nishino I
    • Organizer
      14th International Congress of the World Muscle Society
    • Place of Presentation
      UNI-MAIL, Geneva, Switzerland
    • Year and Date
      2009-09-11
    • Related Report
      2009 Annual Research Report
  • [Presentation] Human PTRF mutations cause secondary deficiency of caveolins resulting in muscular dystrophy with generalized lipodystrophy2009

    • Author(s)
      林由起子
    • Organizer
      14th International Congress of the World Muscle Society
    • Place of Presentation
      UNI-MAIL, Geneva, Switzerland
    • Year and Date
      2009-09-11
    • Related Report
      2009 Annual Research Report
  • [Presentation] Screening the FHL1 mutation in Japanese patients with non-4q35 FSHD2009

    • Author(s)
      Hayashi YK, Goto K, Noguchi S, Nishino I
    • Organizer
      14th International Congress of the World Muscle Society
    • Place of Presentation
      UNI-MAIL, Geneva, Switzerland
    • Year and Date
      2009-09-10
    • Related Report
      2009 Annual Research Report
  • [Presentation] The association of dysferlin and affixin is regulated by calcium concentration2009

    • Author(s)
      Matsuda C, Kameyama K, Nishino I, Hayashi YK
    • Organizer
      14th International Congress of the World Muscle Society
    • Place of Presentation
      UNI-MAIL, Geneva, Switzerland
    • Year and Date
      2009-09-10
    • Related Report
      2009 Annual Research Report
  • [Presentation] Vascular glycogen storage in Pompe disease demonstrated by epon-embedded muscle section2009

    • Author(s)
      Mitsuhashi S, Nonaka I, Noguchi S, Hayashi YK, 他
    • Organizer
      14th International Congress of the World Muscle Society
    • Place of Presentation
      UNI-MAIL, Geneva, Switzerland
    • Year and Date
      2009-09-10
    • Related Report
      2009 Annual Research Report
  • [Presentation] Identification of a novel gene for muscular dystrophy with secondary caveolin deficiency2009

    • Author(s)
      林由起子
    • Organizer
      The 8th French-Japanese Workshop for Muscular Dystrophy
    • Place of Presentation
      Institute of Myology, Paris, France
    • Year and Date
      2009-07-03
    • Related Report
      2009 Annual Research Report
  • [Presentation] 二次性カベオリン欠損症の新規原因遺伝子同定とその臨床病態についての検討2009

    • Author(s)
      林由起子, 三橋里美, 朴英恩, 埜中征哉, 西野一三
    • Organizer
      第50回日本神経学会総会
    • Place of Presentation
      仙台国際センター, 仙台
    • Year and Date
      2009-05-21
    • Related Report
      2009 Annual Research Report
  • [Presentation] 本邦 zaspopathy 症例における臨床筋病理学的検討2009

    • Author(s)
      三橋里美, Shalaby S, 後藤加奈子、埜中征哉, 他
    • Organizer
      第50回日本神経学会総会
    • Place of Presentation
      仙台国際センター, 仙台
    • Year and Date
      2009-05-21
    • Related Report
      2009 Annual Research Report
  • [Presentation] 先天性金線維タイプ不均等症(CFTD)様先天性筋強直性ジストロフィー(CDM)2009

    • Author(s)
      冨永佳代, 林由起子, 後藤加奈子, 南成祐, 他
    • Organizer
      第50回日本神経学会総会
    • Place of Presentation
      仙台国際センター, 仙台
    • Year and Date
      2009-05-20
    • Related Report
      2009 Annual Research Report
  • [Presentation] Cytoplasmic body with acid phosphatase activity-Hallmark of adult-onset Pompe disease on muscle pathology2008

    • Author(s)
      Nishino I, 他
    • Organizer
      Congress of the World Muscle Society (WMS)
    • Place of Presentation
      イギリス
    • Year and Date
      2008-10-01
    • Related Report
      2008 Annual Research Report
  • [Presentation] Distal myopathy in multi-minicore disease2008

    • Author(s)
      Okahashi S, 他
    • Organizer
      Congress of the World Muscle Society (WMS)
    • Place of Presentation
      イギリス
    • Year and Date
      2008-10-01
    • Related Report
      2008 Annual Research Report
  • [Presentation] Novel FHL1 mutations in fatal and benign reducing body myopathy2008

    • Author(s)
      Shalaby S, 他
    • Organizer
      Congress of the World Muscle Society (WMS)
    • Place of Presentation
      イギリス
    • Year and Date
      2008-10-01
    • Related Report
      2008 Annual Research Report
  • [Book] 小児筋疾患診療ハンドブック2009

    • Author(s)
      林由起子
    • Total Pages
      213
    • Publisher
      診断と治療社
    • Related Report
      2009 Annual Research Report
  • [Book] ミオパチー-臨床と治療研究の最前線2009

    • Author(s)
      林由起子
    • Total Pages
      127
    • Publisher
      医歯薬出版株式会社
    • Related Report
      2009 Annual Research Report
  • [Remarks]

    • URL

      http://www.ncnp.go.jp/nin/guide/r1/index.html

    • Related Report
      2009 Annual Research Report

URL: 

Published: 2008-04-01   Modified: 2016-04-21  

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