| Project/Area Number |
17590896
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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 |
HAYASHI Akito Juntendo University, Graduate School of Medicine, Senior Associate Professor, 大学院医学研究科, 准教授 (60180957)
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| Co-Investigator(Kenkyū-buntansha) |
ARIKAWA Eri (HIRASAWA Eri) Juntendo University, Graduate School of Medicine, Senior Associate Professor, 大学院医学研究科, 准教授 (50245718)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | Heparansulfate proteoglycan / Perlecan / Myotonia / therapy / mouse model / パールカン / Schwartz-Jampel症候群 / 筋電図 |
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| Research Abstract |
Schwartz-Jampel syndrome (SJS), characterized by myotonia and mildchondrodysplasiais, is caused by partially functional mutations of perlecan. We previously demonstrated that perlecan is essential for localizing acetylcholinesterase (AChE) to neuromuscular junction (NMJ). To investigate the mechanism of myotonia caused by perlecan defects, we have created a mouse model by rescuing the perinatal lethality of perlecan-null mice by expressing recombinant perlecan specifically in cartilage under the control of a cartilage-specific promoter. The mutant mice survived but developed myotonia, which showed a continuous discharge on the EMG (electromyography) and degeneration of muscle, characteristics to SJS. The discharge was blocked by treatment with curare, an acetylcholine receptor (AChR) blocker. botulinumtoxin type A, which inhibits the release of ACh from the nerve terminal. Curare application reduced myotonia in orbicularis oculi muscles. These results suggest that a combination of these presynaptic abnormalities and postsynaptic muscle defects causes a continuous contraction of perlecan-null muscle. Our mouse model is useful to study the mechanism of myotonia and to develop therapeutic agents for the disease.
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