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A study of pathogenesis for Duchenne muscular dystrophy

杜氏肌营养不良症发病机制的研究

基本信息

批准号：
02454271
负责人：
MIIKE Teruhisa
金额：
$ 2.75万
依托单位：
KUMAMOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1992
项目状态：
已结题

项目摘要

(1) Dystrophin and Dystophin-related protein: To determine the localization and functional significance of dystrophin, we studied various tissues from almost the entire body of control and mdx mice, with immunohistochemically, immunoelectrophoretically, using eight kinds of monoclonal and polyclonal antibodies against dystrophin. We confirmed that dystrophin is really exist on neurons and synapses such as neuromuscular junctions, myotendinous junctions, and intrafusal muscle fibers. We also found dystrophin and its four isoforms on retina with RT-PCR method. The localization of dystrophin in central nervous system and synapses suggests its physiological function in the conduction system rather than a mechanical one. Dystrophin-related protein (DRP) is also exist on the same regions as dystrophin dose. DRP seems to increase on synapses in mdx tissue as compensatory reaction for absent of dystrophin. The result also suggest that dystrophin and DRP have the same physiological function in the conduction system.(2) Nerve growth factor receptor: Immunohistochemical and immunoelectrophoretical studies were performed using nerve growth factor receptor (NGFR) antibody for muscle tissues from patients with muscular dystrophies. The results showed strong NGFR immunoreactivity on the tunica adventitia of blood vessels in biopsied muscle specimens from muscular dystrophy patients, but it was almost absent in specimens from non-diagnostic controls. This suggests a process in the sympathetic nervous system involving blood vessels in muscular dystrophies.(3) Detection of point mutation and carrier: We demonstrated its effectiveness of TOP-analysis to detect nonsense mutations in both DMD-patients and carrier females on material derived from blood samples.

(1)肌营养不良蛋白（Dystrophin）和dystophin相关蛋白：为了确定Dystrophin的定位和功能意义，我们利用免疫组织化学、免疫电泳等方法，对8种抗Dystrophin的单克隆和多克隆抗体进行了对照和mdx小鼠几乎全身的各种组织的研究。我们证实了肌营养不良蛋白确实存在于神经肌肉连接、肌腱连接和肌内纤维等神经元和突触上。我们还用RT-PCR方法在视网膜上发现了肌营养不良蛋白及其四种亚型。肌营养不良蛋白在中枢神经系统和突触中的定位表明其在传导系统中的生理功能而非机械功能。肌营养不良蛋白相关蛋白（DRP）也存在于与肌营养不良蛋白剂量相同的区域。DRP在mdx组织突触上的增加似乎是对肌营养不良蛋白缺失的代偿反应。结果还表明，肌营养不良蛋白和DRP在传导系统中具有相同的生理功能。(2)神经生长因子受体：采用神经生长因子受体（NGFR）抗体对肌营养不良患者的肌肉组织进行免疫组化和免疫电泳研究。结果显示，肌营养不良患者肌肉标本的血管外膜具有较强的NGFR免疫反应性，但在非诊断性对照标本中几乎没有。这表明在肌肉萎缩症中，交感神经系统中有一个涉及血管的过程。(3)点突变和携带者的检测：我们证明了top分析在dmd患者和女性携带者的血液样本中检测无义突变的有效性。