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Role of perlecan at the neuromuscular junction

Research Project

Project/Area Number 14570618
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

HIRASAWA Eri  Juntendo University, School of Medicine, Assistant Professor, 医学部, 講師 (50245718)

Co-Investigator(Kenkyū-buntansha) HIRASAWA Motoyuki  Juntendo University, School of Medicine, assistant, 医学部, 講師 (90338393)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2002: ¥2,500,000 (Direct Cost: ¥2,500,000)
Keywordsperlecan / peparan sulfate proteoglycan / neuromuscular junction / acetylcholine esterase / myotonia / microelectrode analyses / Schwartz-Jampel syndrome
Research Abstract

At the NMJ, the nicotinic ACh receptor mediates postsynaptic depolarization, and acetylcholinesterase (AChE) terminates this process by hydrolyzing ACh. Efficient and accurate synaptic transmission requires proper localization of many signaling proteins in the synaptic membrane. In the perlecan knockout mice, muscle development and differentiation appear to be normal and normal nerve terminals are formed at birth. Clustering molecules are present at the NMJ of the mutant mouse muscles. However, AChE is absent at the newborn MNJ, although AChE protein is synthesized normally. An animal model is ideal to study the mechanism of myotonia of SJS(Schwartz-Jampel syndrome). However, perlecan-null mice are lethal. To overcome this problem, we used a genetic approach to rescue the perinatal lethal phenotype of perlecan-null mice by mating heterozygotes of perlecan-null mice with transgenic mice expressing recombinant perlecan specifically to cartilage but not to other tissues. The perlecan-null homozygous mice with the transgene are born normal and survive, but they develop small eyes and blepharospasm, common features of SJS. These mice also show myotonic discharge in electromyography (EMG) and myopathic change in histology. AChE activity staining shows reduced localization of AChE at the NMJ in the mutant. mice. Thus, the rescued mice show phenotypes characteristic of SJS and are useful as an animal model to study the mechanism of myotonia and to develop therapeutic agents for the disease.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Arikawa-Hirasawa E, Rossi SG, Rotundo RL, Yamada Y: "Absence of acetylcholinesterase at the neuromuscular junctions of perlecan-null mice."Nature Neuroscience. 5. 119-123 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Arikawa-Hirasawa E, Le AH, Nishino I, Nonaka I, Ho NC et al.: "Structural and functional mutations of the perlecan gene cause Schwartz-Jampel syndrome, with myotonic myopathy and chondrodysplasia."Am.J.Hum.Gen.. 70. 1368-1375 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Arikawa-Hirasawa E, Wilcox WR, Yamada Y: "Dyssegmental Dysplasia, Silverman-Handmaker Type : Unexpected role of perlecan in cartilage development."Am.J.Med.Gen.. 106. 254-257 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hassell J, Yamada Y, Arikawa-Hirsawa E: "Role of perlecan in skeletal development and diseases."Glycoconj J. 19(4/5). 263-267 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yuasa K, Fukumoto S, Kamasaki Y, et al.: "Laminin alpha2 essential for odontoblast differentiation regulating dentin sialoprotein expression"J Biol Chem.. 279. 10286-10292 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hirasawa M, Ohshima T, Takahashi S, et al.: "Perinatal abrogation of Cdk5 expression in brain results in neuronal migration defects"Proc Natl Acad Sci U S A.. 101(16). 6249-6254 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Arikawa-Hirasawa E, Rossi SG, Rotundo RL, Yamada Y.: "Absence of acetyicholinesterase at the neuromuscular junctions of perlecan-null mice."Nature Neuroscience. 5. 119-123 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Arikawa-Hirasawa E, Le AH, Nishino I, Nonaka I, Ho NC Francomano CA, Govindraj P, Hassell JR, Devaney JM, Spranger J, Stevenson RH, Iannaccone S, Dalakas MC, Yamada Y.: "Structural and functional mutations of the perlecan gene cause Schwartz-Jampel syndrome, with myotonic myopathy and chondrodysplasia."Am.J.Hum.Gen.. 70. 1368-1375 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Arikawa-Hirasawa E, Wilcox WR, Yamada Y.: "Dyssegmental Dysplasia, Silverman-Handmaker Type: Unexpected role of perlecan in cartilage development."Am.J.Med.Gen.. 106. 254-257 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hassell J, Yamada Y, Arikawa-Hirasawa E.: "Role of perlecan in skeletal development and diseases."Glycoconj J.. 19(4/5). 263-267 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yuasa K, Fukumoto S, Kamasaki Y, Yamada A, Fukumoto E, Kanaoka K, Saito K, Harada H, Arikawa-Hirasawa E, Miyagoe-Suzuki Y, Takeda S, Okamoto K, Kato Y, Fujiwara T.: "Laminin alpha2 essential for odontoblast differentiation regulating dentin sialoprotein expression."J Biol Chem.. 279. 10286-10292 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hirasawa M, Ohshima T, Takahashi S, Longenecker G, Honjo Y, Veeranna, Pant HC, Mikoshiba K, Brady RO, Kulkarni AB.: "Links Perinatal abrogation of Cdk5 expression in brain results in neuronal migration defects"Proc Natl Acad Sci U S A 2004 Apr 20. 101(16). 6249-6254 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Arikawa-Hirasawa E, Le AH, Nishino I, et al.: "Structural and functional mutations of the perlecan gene cause schwartz-jampel syndrome, with myotonic myopathy and chondrodysplasia"American Journal of Human Genetics. 70. 1368-1375 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Arikawa-Hirasawa E, Rossi SG, Rotundo, RL, Yamada Y.: "Absence of acetylcholinesterase at the neuromuscular junctions of perlecan-null mice"Nature Neuroscience. 5(2). 119-123 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Arikawa-Hirasawa E, Yamada Y: "Perlecan mutations in mice and humans : critical role of perlecanin skeletal development and disease"Acta myologica. XXSeptember. 134-137 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Arikawa-Hirasawa E, Wilcox WR, Yamada Y: "Dyssegmental Dysplasia, Silverman-Handmaker Type : Unexpected role of perlecan in cartilage development."American Journal of Medical Genetics. 106. 254-257 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hassell J, Yamada Y, Arikawa-Hirasawa E.: "Role of perlecan in skeletal development and diseases."Glycoconj J.. 19(4/5). 263-267 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yuasa K, Fukumoto S, Kamasaki Y, et al.: "Laminin alpha2 essential for odontoblast differentiation regulating dentin sialoprotein expression"J Biol Chem.. 279(11). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Arikawa-Hirasawa E, Le AH, Nishino I, et al.: "Structural and functional mutations of the perlecan geno cause schwartz-jampel syndrome, with myotonic and chondrodysplasia"American Journal of Human Genetics. 70. 1368-1375 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Arikawa-Hirasawa E, Rossi SG, Rotundo, RL, Yamada Y.: "Absence of acetylcholinesterase at the neuromuscular junctions of perlecan-null mice"Nature Neuroscience. 5(2). 119-123 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Arikawa-Hirasawa E, Yamada Y: "Perlecan mutations in mice and humans : critical role of perlecanin skeletal development and disease"Acta myologica. XXSeptember. 134-137 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Arikawa-Hirasawa E, Wilcox WR, Yamada Y: "Dyssegmental Dysplasia, Silverman-Handmaker Type : Unexpected role of perlecan in cartilage development"American Journal of Medical Genetics. 106. 254-257 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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