Study for pathogenesis of Schwartz-Jampel syndrome using mouse model.

利用小鼠模型研究 Schwartz-Jampel 综合征的发病机制。

• 批准号: 17590896
• 负责人: HAYASHI Akito
• 金额: $ 2.18万
• 依托单位: Juntendo University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590896/
• 关键词: Heparansulfate proteoglycan; Perlecan; Myotonia; therapy; mouse model; パールカン; Schwartz-Jampel症候群; 筋電図

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.

Schwartz-Jampel综合征（Schwartz-Jampel syndrome，SJS）是由串珠蛋白聚糖部分功能突变引起的，以肌强直和轻度软骨发育不良为特征。我们以前证明，串珠素是必不可少的本地化乙酰胆碱酯酶（AChE）的神经肌肉接头（NMJ）。为了研究串珠蛋白聚糖缺陷引起的肌强直的机制，我们通过在软骨特异性启动子的控制下在软骨中特异性表达重组串珠蛋白聚糖来挽救串珠蛋白聚糖缺失小鼠的围产期致死性，从而建立了小鼠模型。突变小鼠存活，但发展为肌强直，其在EMG（肌电图）上显示连续放电和肌肉变性，这是SJS的特征。用箭毒（一种乙酰胆碱受体（AChR）阻断剂）治疗可阻断放电。A型肉毒杆菌毒素，其抑制ACh从神经末梢的释放。箭毒应用减少眼轮匝肌强直。这些结果表明，这些突触前异常和突触后肌肉缺陷的组合导致串珠素缺失肌肉的连续收缩。该模型可用于研究肌强直的发病机制和开发治疗药物。

项目成果

Clinical studies for Stiff-person syndrome

僵人综合症的临床研究

• 发表时间: 2006
• 期刊: Sinkei-Naika 64(4)
• 作者: Obata Y;Niikura T;Kanekura K;Hashimoto Y;Kawasumi M;Kita Y;Aiso S;Matsuoka M;Nishimoto I.;Kazuo Yamashiro et al.;Maruyama M;Akito Hayashi.
• 通讯作者: Akito Hayashi.

Targeting perlecan in human keratinocytes reveals novel roles for perlecan in epidermal formation

• DOI: 10.1074/jbc.m509500200
• 发表时间: 2006-02-24
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Sher, I;Zisman-Rozen, S;Ron, D
• 通讯作者: Ron, D

Autophagic Vacuoles with Sarcolemmal Features Delineate Danon Disease and Related Myopathies

• DOI: 10.1097/01.jnen.0000166130.35907.14
• 发表时间: 2005-06
• 期刊: JNEN: Journal of Neuropathology & Experimental Neurology
• 作者: K. Sugie;S. Noguchi;Y. Kozuka;E. Arikawa-Hirasawa;Mikihito Tanaka;Chuanzhu Yan;P. Saftig;K. von Figura;M. Hirano;S. Ueno;I. Nonaka;I. Nishino

わが国におけるジストニー治療の現況

日本肌张力障碍治疗现状

• 发表时间: 2005
• 期刊: 臨床神経 45
• 作者: 目崎高広;林 明人;中瀬浩史;長谷川一子
• 通讯作者: 長谷川一子

若年発症のmyokymia-cramp症候群の一例.

年轻发病的肌颤痉挛综合征一例。

• 发表时间: 2006
• 期刊: 運動障害 16・1
• 作者: 宮元伸和;林明人
• 通讯作者: 林明人