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

Dystrophin是一种420kD的细胞骨架蛋白，在X连锁Duchenne肌营养不良症中是缺陷的。抗dystrophin C-末端结构域的多克隆抗体与一个420kD的dystrophin相关蛋白(DRP)反应，该蛋白位于人类和小鼠的6号染色体上。在dystrophin缺陷的MDX肌肉中可以看到DRP的过度表达。用一种针对预测的DRP氨基酸序列的特异性抗体证实了这些结果。我们研究了DRP在对照小鼠肌肉中表达的发育规律。DRP在胚胎中高度表达，此后逐渐减少。与DRP不同的是，肌营养不良蛋白在胎儿肌肉中没有表达，而是在出生后2天出现，此后含量显著增加。DRP和dystrophin的这种相互表达表明DRP是胎儿骨骼肌中dystrophin的一种亚型。DRP与dystrophin具有相似的分子质量和定位，但在洗涤剂处理后溶解不同。因此，DRP和dystrophin的物理化学性质应该有微小但明显的差异。DRP在营养不良肌肉中的过度表达可能预防或延缓疾病的发生。

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.