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2005 Fiscal Year Final Research Report Summary

THE RELEVANCE OF THE SELECTIVE DAMAGE OF PURKINJE FIBER AND THE ABNORMAL ELECTROCARDIOGRAM IN CANINE X-LINKED MUSCLAR DYSTROPHY

Research Project

Project/Area Number 16500283
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Laboratory animal science
Research InstitutionNATIONAL CENTER OF NEUROLOGY AND PSYCHIATRY (NCNP)

Principal Investigator

SHIMATSU Yoshiki  NCNP, DEPARTMENT OF MOLECULAR THERAPY, SECTION CHIEF, 遺伝子疾患治療研究部, 室長 (90373406)

Co-Investigator(Kenkyū-buntansha) KUWAHARA Masayoshi  THE UNIVERSITY OF TOKYO, GRADUATE SCHOOL OF AGRICULTURAL AND LIFE SCIENCES, ASSISTANT PROFESSOR, 大学院・農学生命科学研究科, 助教授 (30205273)
WAKAO Yoshito  AZABU UNIVERSITY, SCHOOL OF VETERINARY MEDICINE, PROFESSOR, 獣医学部, 教授 (20063969)
TAKEDA Shin'ichi  NCNP, DEPARTMENT OF MOLECULAR THERAPY, DIRECTOR, 遺伝子疾患治療研究部, 部長 (90171644)
Project Period (FY) 2004 – 2005
Keywordsmuscular dystrophy / canine X-linked muscular dystrophy / purkinje fiber / vacuolar degeneration / MuRF-1 / cardiac conduction / μ-calpain / ubiquitin
Research Abstract

In Duchenne muscle dystrophy (DMD), increase in the number of patients who die with the cardiac failure instead of the respiratory is recognized. There is a reason why the death rate of the respiratory decreases in the diffusion of respirators. A beagle based colony of canine X-linked muscular dystrophy (CXMD) dog in Japan designated CXMD_J shows skeletal muscle atrophy and weakness which is similar to DMD. Our main research subject has been to clear the mechanism of myocardial involvement in DMD using the CXMD_J dog. It doubted that the CXMD_J dog had the cardiac conduction abnormality since an abnormal Q wave of electrocardiogram and a sudden death due to the lethal arrhythmia were recognized. In the present study, the histopathological and immunohistochemical examination and the molecular determination after micro-dissection in the purkinje fiber were carried out. 1.The vacuolar degeneration of purkinje fiber was already observed before the working myocardium was involved. 2.The accumulation of calcium-dependent proteolysis, μ-calpain was observed in the purkinje fiber. 3.The cardiac Troponin I (cTnI) which was a substrate of μ-calpain was fragmented by μ-calpain and was isolated in the serum. 4.The cTnI which was a E3 ubiquitin ligase was fragmented by μ-calpain, and was ubiquitinated by the muscle-specific RING finger protein 1 (MuRF1) related to the skeletal muscle atrophy. The results of the present study suggest that the vacuolar degeneration of purkinje fiber in the CXMD_J dog was caused by the cTnI, and the cTnI was fragmented by the accumulation of μ-calpain and was broken down by the ubiquitin-proteasome pathway after the ubiquitination of MuRF1.

  • Research Products

    (11 results)

All 2005 2004

All Journal Article (11 results)

  • [Journal Article] Major clinical and histopathological characteristics of canine X-linked muscular dystrophy in Japan, CXMD_J.2005

    • Author(s)
      Shimatsu Y et al.
    • Journal Title

      Acta Myol 24・2

      Pages: 145-154

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Intracellular localization of dysferlin and its association with the dihydropyridine receptor.2005

    • Author(s)
      Ampong BN et al.
    • Journal Title

      Acta Myol 24・2

      Pages: 134-144

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Bone marrow stromal cells generate muscle cells and repair muscle degeneration.2005

    • Author(s)
      Dezawa M et al.
    • Journal Title

      Science 309・5732

      Pages: 314-317

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Epsilon-sarcoglycan compensates for lack of alpha-sarcoglycan in a mouse model of limb-girdle muscular dystrophy.2005

    • Author(s)
      Imamura M et al.
    • Journal Title

      Hum Mol Genet 14・6

      Pages: 775-783

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Major clinical and histopathological characteristics of canine X-linked muscular dystrophy in Japan, CXMD_J.2005

    • Author(s)
      Shimatsu Y, Yoshimura M, Yuasa K, Urasawa N, Tomohiro M, Nakura M, Tanigawa M, Nakamura A, Takeda S.
    • Journal Title

      Acta Myol 24-2

      Pages: 145-154

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Intracellular localization of dysferlin and its association with the dihydropyridine receptor.2005

    • Author(s)
      Ampong BN, Imamura M, Matsumiya T, Yoshida M, Takeda S.
    • Journal Title

      Acta Myol 24-2

      Pages: 134-144

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Bone marrow stromal cells generate muscle cells and repair muscle degeneration.2005

    • Author(s)
      Dezawa M, Ishikawa H, Itokazu Y, Yoshihara T, Hoshino M, Takeda S, Ide C, Nabeshima Y.
    • Journal Title

      Science 309-5732

      Pages: 314-317

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Epsilon-sarcoglycan compensates for lack of alpha-sarcoglycan in a mouse model of limb-girdle muscular dystrophy.2005

    • Author(s)
      Imamura M, Mochizuki Y, Engvall E, Takeda S
    • Journal Title

      Hum Mol Genet 14-6

      Pages: 775-783

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] AAV vector-mediated microdystrophin expression in a relatively small percentage of mdx myofibers improved the mdx phenotype.2004

    • Author(s)
      Yoshimura M et al.
    • Journal Title

      Mol Ther 10・5

      Pages: 821-828

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 「進化」する疾患モデル動物,第8回筋ジストロフィーのモデル動物2004

    • Author(s)
      島津美樹, 武田伸一
    • Journal Title

      細胞工学 23・9

      Pages: 1082-1085

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] AAV vector-mediated microdystrophin expression in a relatively small percentage of mdx myofibers improved the mdx phenotype.2004

    • Author(s)
      Yoshimura M, Sakamoto M, Ikemoto M, Mochizuki Y, Yuasa K, Miyagoe-Suzuki Y, Takeda S.
    • Journal Title

      Mol Ther 10-5

      Pages: 821-828

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2007-12-13  

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