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Role of dystrophin-related protein in the pathogenesis of Duchenne muscular dystrophy.

肌营养不良蛋白相关蛋白在杜氏肌营养不良症发病机制中的作用。

基本信息

批准号：
04670508
负责人：
ISHIURA Shoichi
金额：
$ 0.45万
依托单位：
Institute of Molecular and Cellular Biosciences, The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1993
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04670508/
关键词：
Dystrophy Dystrophin treatment

项目摘要

Dystrophin is a 420kD cytoskeletal protein and is defective in X-linked Duchenne muscular dystrophy. Polyclonal antibody against the C-terminal domain of dystrophin reacted with a 420kD dystrophin-related protein (DRP), which maps to chromosome 6 in human as well as in mouse. Overexpression of DRP was seen in dystrophin-deficient mdx muscles. These results were confirmed by using a specific antibody raised against predicted amino acid sequences of DRP.We investigated the developmental regulation of DRP expression in control mouse muscles. DRP is highly expressed in embryos and gradually decreased thereafter. In contrast to DRP, dystrophin is not demonstrated in fetal muscles, but rather appeared at 2 days after birth, after which a significant increase in content was observed. This reciprocal expression of DRP and dystrophin suggests that DRP is an isoform of dystrophin in fetal skeletal muscle.DRP has a similar molecular mass and localization as dystrophin, but is solubilized differently after detergent treatment. Therefore, there should be minor but distinct differences in physicochemical properties of DRP and dystrophin. Overexpression of DRP in dystrophic muscles may prevent or retard the onset of the disease.

肌营养不良蛋白是一种420kD的细胞骨架蛋白，在x连锁杜氏肌营养不良症中存在缺陷。抗肌营养不良蛋白c端多克隆抗体与一个420kD的肌营养不良蛋白相关蛋白（DRP）反应，该蛋白位于人类和小鼠的6号染色体上。DRP在肌营养不良蛋白缺乏的mdx肌肉中过表达。这些结果通过针对预测的DRP氨基酸序列的特异性抗体得到了证实。我们研究了对照小鼠肌肉中DRP表达的发育调控。DRP在胚胎中高表达，此后逐渐降低。与DRP相反，肌营养不良蛋白在胎儿肌肉中没有表现出来，而是在出生后2天出现，之后含量显著增加。DRP和肌营养不良蛋白的相互表达表明DRP是胎儿骨骼肌中肌营养不良蛋白的一种同型。DRP与肌营养不良蛋白具有相似的分子质量和定位，但经过洗涤剂处理后的溶解性不同。因此，DRP和肌营养不良蛋白的理化性质应该有细微但明显的差异。DRP在营养不良肌肉中的过度表达可以预防或延缓疾病的发生。