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Studies on pathophysiology and experimental therapy of Ullrich's disease with collagen VI deficiency.

Research Project

Project/Area Number 16590837
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionKagoshima University

Principal Investigator

HIGUCHI Itsuro  Kagoshima University, University Hospital, Faculty of Medicine and Dentistry, Assistant Professor, 医学部・歯学部附属病院, 講師 (80183573)

Co-Investigator(Kenkyū-buntansha) TAKASHIMA Hiroshi  Kagoshima University, Graduate School of Medical and Dental Sciences, Research Associate, 大学院・医歯学総合研究科, 助手 (80372803)
OSAME Mitsuhiro  Kagoshima University, Graduate School of Medical and Dental Sciences, Professor, 大学院・医歯学総合研究科, 教授 (10041435)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
KeywordsUllrich's disease / Bethlem myopathy / collagen VI / collagenopathy / laminin β1 / NG2 proteoglycan / experimental therapy / tenascin C / CD44 / 実験的治療 / laminin β1
Research Abstract

Collagenopathies with collagen VI mutations include Ulirich congenital muscular dystrophy (Ullrich's disease) and Bethlem myopathy. Patients with Ullrich's disease have generalized muscle weakness, multiple contractures of the proximal joints and hyperextensibility of the distal joints. Bethlem myopathy is characterized by the combination of proximal muscle weakness and contractures of finger, elbow, and ankle joints. We found for the first time a deficiency of collagen VI in Ullrich's disease. Furthermore, we found an abnormality of cell adhesion and abnormal regeneration or maturation in Ullrich's disease. Mutations in the genes COL6A1, COL6A2, COL6A3 are associated with Ullrich's disease and Bethlem myopathy. Bethlem myopathy is inherited in an autosomal dominant manner and Ullrich's disease usually in an autosomal recessive manner. Recently, de novo dominant mutations are reported in Ullrich's disease. We evaluated the role of nonsense-mediated mRNA decay (NMD) in Ullrich's disease that has a frameshift mutation with a premature termination codon in the COL6A2 gene causing the loss of collagen VI. The pharmacological block of NMD caused upregulation of the mutant collagen VI and partially functional extracellular matrix formation. Our results suggest that NMD inhibitors can be used as a therapeutic tool to rescue some human genetic diseases exacerbated by NMD.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (5 results)

All 2006 2004

All Journal Article (5 results)

  • [Journal Article] Abnormal expression of proteoglycans in Ullrich's disease with collagen VI deficiency.2006

    • Author(s)
      Higashi K, Higuchi I et al.
    • Journal Title

      Muscle & Nerve 33・1

      Pages: 120-126

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Abnormal expression of proteoglycans in Ullrich's disease with collagen VI deficiency.2006

    • Author(s)
      Higashi K, Higuchi I et al.
    • Journal Title

      Muscle & Nerve 33(1)

      Pages: 120-126

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Abnormal expression of proteoglycans in Ullrich's disease with collagen VI deficiency.2006

    • Author(s)
      Higashi et al.
    • Journal Title

      Muscle & Nerve 33・1

      Pages: 120-126

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Inhibition of nonsense-mediated mRNA decay rescues the phenotype in Ullrich's disease.2004

    • Author(s)
      Usuki F et al.
    • Journal Title

      Annals of Neurology 55・5

      Pages: 740-744

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Inhibition of nonsense-mediated mRNA decay rescues the phenotype in Ullrich's disease.2004

    • Author(s)
      Usuki F et al.
    • Journal Title

      Annals of Neurology 55(5)

      Pages: 740-744

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary

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Published: 2004-04-01   Modified: 2016-04-21  

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