Arahata K, Beggs A H, Honda H, Ito S, Ishiura S, Tsukahara T, Ishiguro T, Eguchi C, Orimo S, Arikawa E
National Institute of Neuroscience, NCNP, Tokyo, Japan.
J Neurol Sci. 1991 Feb;101(2):148-56. doi: 10.1016/0022-510x(91)90039-a.
Duchenne muscular dystrophy (DMD) is a fatal X-linked recessive disorder of muscle in children. The DMD gene product, "dystrophin", is absent from DMD, while the allelic disease, Becker muscular dystrophy (BMD), exhibits dystrophin of abnormal size and/or quantity. But we are still uncertain about the scenario that internally deleted (or duplicated) dystrophin in BMD possesses its carboxy (C)-terminal region, and severely truncated dystrophin in DMD does not. Here we use a new monoclonal antibody directed against an peptide in the C-terminal end of the dystrophin molecule to show that the C-terminus is preserved in 30 BMD and 24 control skeletal muscles but not in 21 DMD specimens. This result, taken together with data on deletions of the dystrophin gene, emphasizes both the diagnostic and biological importance of the C-terminal domain which is required for proper function and stability of dystrophin, and substantiates the validity of the reading frame hypothesis for DMD versus BMD deletions on a biochemical level.
杜氏肌营养不良症（DMD）是一种致命的儿童X连锁隐性肌肉疾病。DMD患者体内缺乏DMD基因产物“抗肌萎缩蛋白”，而等位基因疾病贝氏肌营养不良症（BMD）则表现出大小和/或数量异常的抗肌萎缩蛋白。但我们仍不确定BMD中内部缺失（或重复）的抗肌萎缩蛋白是否保留了其羧基（C）末端区域，而DMD中严重截短的抗肌萎缩蛋白却没有。在这里，我们使用一种针对抗肌萎缩蛋白分子C末端肽段的新型单克隆抗体，结果表明C末端在30个BMD样本和24个对照骨骼肌样本中得以保留，但在21个DMD样本中则没有。这一结果，结合抗肌萎缩蛋白基因缺失的数据，既强调了C末端结构域在抗肌萎缩蛋白正常功能和稳定性方面的诊断及生物学重要性，也在生化水平上证实了DMD与BMD缺失的读码框假说的有效性。
