Sewry C A, Matsumura K, Campbell K P, Dubowitz V
Department of Paediatrics and Neonatal Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London, U.K.
Neuromuscul Disord. 1994 Sep-Nov;4(5-6):401-9. doi: 10.1016/0960-8966(94)90079-5.
The expression of dystrophin, the dystrophin-associated proteins and utrophin has been studied immunocytochemically in three young, manifesting carriers of Duchenne muscular dystrophy, aged 3, 5 and 12 yrs, one adult manifesting carrier, aged 60 yrs, and one presumptive carrier with a raised serum creatine kinase, aged 24 yrs, the mother of the 5-yr-old manifesting carrier. The manifesting carriers had variable degrees of weakness; the presumptive carrier had no weakness. Morphological abnormalities were also variable and were most marked in the young manifesting carriers. The three young manifesting carriers and the presumptive carrier had a mosaic pattern of dystrophin-positive and dystrophin-negative fibres. All the dystrophin-associated proteins were reduced in the dystrophin-deficient fibres, giving a similar mosaic pattern to dystrophin. Expression of dystrophin and the dystrophin-associated proteins was normal in the adult manifesting carrier. Utrophin was detected on the sarcolemma of fibres both with and without dystrophin and the dystrophin-associated proteins. Thus, dystrophin and utrophin are co-expressed in several fibres in carriers. The results emphasize the close association between dystrophin and the glycoprotein complex and their role in the pathogenesis of muscle damage. In addition, the presence of utrophin in fibres with greatly reduced glycoproteins suggests that very little of the glycoprotein complex may be required to anchor the amount of utrophin expressed at the sarcolemma in these particular cases.
运用免疫细胞化学方法，对3名杜氏肌营养不良症的显性携带者（年龄分别为3岁、5岁和12岁）、1名60岁的成年显性携带者以及1名血清肌酸激酶升高的推定携带者（为5岁显性携带者的24岁母亲）进行了肌营养不良蛋白、肌营养不良蛋白相关蛋白及抗肌萎缩蛋白的表达研究。显性携带者有不同程度的肌无力；推定携带者无肌无力症状。形态学异常也各不相同，在年轻的显性携带者中最为明显。3名年轻的显性携带者和推定携带者均呈现肌营养不良蛋白阳性和阴性纤维的镶嵌模式。在缺乏肌营养不良蛋白的纤维中，所有肌营养不良蛋白相关蛋白均减少，呈现出与肌营养不良蛋白相似的镶嵌模式。成年显性携带者中肌营养不良蛋白和肌营养不良蛋白相关蛋白的表达正常。在有和没有肌营养不良蛋白及肌营养不良蛋白相关蛋白的纤维肌膜上均检测到了抗肌萎缩蛋白。因此，在携带者的若干纤维中，肌营养不良蛋白和抗肌萎缩蛋白共同表达。这些结果强调了肌营养不良蛋白与糖蛋白复合物之间的密切关联及其在肌肉损伤发病机制中的作用。此外，在糖蛋白大幅减少的纤维中存在抗肌萎缩蛋白，这表明在这些特定情况下，可能只需极少的糖蛋白复合物就能锚定在肌膜上表达的抗肌萎缩蛋白量。
