2003 Fiscal Year Final Research Report Summary
Role of perlecan at the neuromuscular junction
| Project/Area Number |
14570618
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Juntendo University |
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Principal Investigator |
HIRASAWA Eri Juntendo University, School of Medicine, Assistant Professor, 医学部, 講師 (50245718)
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| Co-Investigator(Kenkyū-buntansha) |
HIRASAWA Motoyuki Juntendo University, School of Medicine, assistant, 医学部, 講師 (90338393)
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| Project Period (FY) |
2002 – 2003
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| Keywords | perlecan / peparan sulfate proteoglycan / neuromuscular junction / acetylcholine esterase / myotonia / microelectrode analyses / Schwartz-Jampel syndrome |
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| 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.
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[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)
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[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)
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「研究成果報告書概要(欧文)」より
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