Hoffman E P, Knudson C M, Campbell K P, Kunkel L M
Department of Pediatrics, Harvard Medical School, Boston, Massachusetts.
Nature. 1987;330(6150):754-8. doi: 10.1038/330754a0.
Duchenne muscular dystrophy (DMD) is a human X-linked biochemical defect resulting in the progressive wasting of skeletal muscle of affected individuals. It is the most common and is considered to be the most devastating of the muscular dystrophies, affecting about 1 in 3,500 live-born males. The gene that, when defective, results in this disorder was recently isolated. Using the cloned complementary DNA sequences corresponding to the DMD gene, antibodies have been produced that react with a protein species of relative molecular mass (Mr) approximately 400,000 (400K) which was absent in two DMD-affected individuals and in mdx mice. This protein species is called dystrophin because of its identification by molecular-genetic analysis of affected individuals. Here we show that dystrophin is associated with the triadic junctions in skeletal muscle, and is therefore probably involved with Ca2+ homoeostasis. We also show that the approximately 450K ryanodine receptor/sarcoplasmic reticulum Ca2+ channel, which has the large size and subcellular distribution characteristics of dystrophin, is an immunologically distinct protein species.
杜兴氏肌营养不良症（DMD）是一种人类X连锁生化缺陷病，会导致受影响个体的骨骼肌进行性萎缩。它是最常见的，也被认为是最具破坏性的肌营养不良症，约每3500名活产男婴中就有1人患病。导致这种疾病的缺陷基因最近已被分离出来。利用与DMD基因对应的克隆互补DNA序列，已产生了能与一种相对分子质量（Mr）约为400,000（400K）的蛋白质发生反应的抗体，该蛋白质在两名DMD患者和mdx小鼠中不存在。由于通过对受影响个体的分子遗传学分析确定了这种蛋白质，所以将其称为抗肌萎缩蛋白。我们在此表明，抗肌萎缩蛋白与骨骼肌中的三联体连接有关，因此可能参与钙稳态。我们还表明，具有抗肌萎缩蛋白的大小和亚细胞分布特征的约450K的兰尼碱受体/肌浆网钙通道是一种免疫上不同的蛋白质。
