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Clarification of pathomechanism of inherited muscular disorder due to abnormality of sarcomeric proteins

Research Project

Project/Area Number 18590964
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionNational Center of Neurology and Psychiatry

Principal Investigator

MINAMI Narihiro  National Center of Neurology and Psychiatry, National Institute of Neuroscience, Depertment of Neuromuscular Research, Adjunct Researcher (20392417)

Co-Investigator(Kenkyū-buntansha) NISHINO Ichizo  National Institute of Neuroscience, Depertment of Neuromuscular Research, Director (00332388)
HAYASHI Yukiko  National Institute of Neuroscience, Depertment of Neuromuscular Research, Section chief (50238135)
NOGUCHI Satoru  National Institute of Neuroscience, Depertment of Neuromuscular Research, Section chief (00370982)
NONAKA Ikuya  National Institute of Neuroscience, Honorary member (80040210)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,890,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsNeuromuscular disorders / sarcomere / calpain 3 / cDNA microarray / myofibrillar myopathy / myotilin / ZASP / limb-girdle muscular dystrophy / 臨床遺伝学 / ミオフィブリラーミオパチー / マルチミニコア / myotilin / 拡張型心筋症 / 分子病理学 / ミオフィプリラーミオパチー
Research Abstract

1. cDNA microarray analysis of calpainopathy Muscles from calpainopathy patients show focal necrosis and regeneration at earlier stage, but lobukted fiber formation at later chronic stage. We compared the gene expression profiles of these two stages with control muscles using a cDNA microarray customized for skeletal muscle specific genes. We identified 29 genes whose mRNA expression were specifically altered in muscles with lobulated fibers, especially the genes of actin regulatory proteins, including gelsolin, PDLIM3 and troponin I1. We proposed that abnormal gene expression for actin regulatory proteins may contribute to alter myofibril organization, showing lobulated fibers.
2. Mutation analysis and characterization of myofibrillar myopathy(MFM) MFM is a group of disorders based on histopathological features, showing myofibrillar disorganization with protein aggregates. This is the first large-scale of genetic study of MFM in Japan. (1) We selected 47 patients whose muscle pathology is consistent with MFM. We found one patient with desmin gene mutation, but no patient had mutations in αB-crystallin, ZASP and myotilin genes, This result suggests that most of the Japanese MFM patients may have mutations in the gene(s) still yet unidentified. (2) ZASP mutations can show various clinical features. Thus, we examined ZASP mutation in 200 patients showing disorganization of intermyofibrillar networks as a major pathological feature. One patient with high CKemia and three patients who were clinically diagnosed to have sIBM had mutations in ZASP. Interestingly, multi-minicores were the most striking pathological finding in the skeletal muscle from one of the patients. This is the first report that zaspopathy can cause multi-minicores. (3) We also found the first Japanese limb-girdle muscular dystrophy type 1A due to myotilin gene mutation. (4) We chose cofilin 2 as a candidate gene for MFM, but no mutation was found in 80 patients.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (8 results)

All 2007

All Journal Article (2 results) (of which Peer Reviewed: 1 results) Presentation (6 results)

  • [Journal Article] Characterization of lobulated fibers in limb girdle muscular dystrophy type 2A by gene expression profiling.2007

    • Author(s)
      Keira Y, et. al.
    • Journal Title

      Neuroscience Research 57

      Pages: 513-521

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Characterization of lobulated fibers in limb girdle muscular dystrophy type 2A by gene expression profiling.2007

    • Author(s)
      Yoko Keira, et al.
    • Journal Title

      Neuroscience Research 57(4)

      Pages: 513-521

    • Related Report
      2006 Annual Research Report
  • [Presentation] Zaspopathy with multi-minicores.2007

    • Author(s)
      Shalaby S, et. al.
    • Organizer
      The 12th International World Muscle Society Congress
    • Place of Presentation
      GIARDINI NAXOS,Italy
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] A novel myotilin mutation in exon 9 〜first LGMD1A in Japan〜.2007

    • Author(s)
      Shalaby S, et. al.
    • Organizer
      The 12th International World Muscle Society Congress
    • Place of Presentation
      GIARDINI NAXOS,Italy
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Zaspopathy with multi-minicores.2007

    • Author(s)
      Shalaby S, et. al.
    • Organizer
      The 12th International World Muscle Society Congress
    • Place of Presentation
      GIARDINI NAXOS, Italy
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] A novel myotilin mutation in exon 9 〜fiist LGMD1A in Japan〜.2007

    • Author(s)
      Shalaby S, et. al.
    • Organizer
      The 12th International World Muscle Society Congress
    • Place of Presentation
      GIARDINI NAXOS, Italy
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Zaspopathy with multi-minicores2007

    • Author(s)
      S Shalaby, et. al.
    • Organizer
      The 12th International World Muscle Society Congress
    • Place of Presentation
      GIARDINI NAXOS, Italy
    • Related Report
      2007 Annual Research Report
  • [Presentation] Anovel myotihn mqtation in exon 9 〜first LGMD1A in Japan〜2007

    • Author(s)
      S Shalaby, et. al.
    • Organizer
      The 12th Intemational World Muscle Sodety Congress
    • Place of Presentation
      GIARDINI NAXOS, Italy
    • Related Report
      2007 Annual Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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