Torelli S, Sogos V, Ennas M G, Muntoni F, Clerk A, Strong P N, Gremo F
Department of Cytomorphology, School of Medicine, Cagliari, Italy.
J Neurosci Res. 1992 May;32(1):116-25. doi: 10.1002/jnr.490320114.
Dystrophin, the protein product defective in Duchenne muscular dystrophy (DMD), is present in all types of muscle and in the brain. The function of the protein is unknown and its role in the brain is unclear, although 30% of DMD patients show nonprogressive mental retardation. We have therefore studied the localisation of dystrophin in cultures of normal and DMD human fetal neurons using antibodies raised to different regions of the protein. Dystrophin immunoreactivity was demonstrated in the soma and axon hillock of normal neurons and appeared to be associated with the inner part of the cell membrane, although some intracellular staining was also observed. Positive dystrophin staining was present only in cells with fully developed neuronal features, although not all the neurons were positive. Glial cells were always negative for the antigen. Immunostaining with antibodies to the brain spectrins indicate that the dystrophin antibodies did not crossreact with these proteins. The possibility of cross-reactivity with other proteins is discussed. Studies of cells cultured from a DMD fetus also showed specific dystrophin immunostaining in neurons, although the muscle was generally negative for dystrophin. However, the localisation of dystrophin immunostaining and that of the brain spectrins and neurofilaments appeared abnormal, as did the overall morphology of the cells. This suggests that dystrophin may play a role during brain development and dystrophin deficiency results in abnormal neuronal features. This would be consistent with the nonprogressive nature of the mental retardation observed in DMD patients.
肌营养不良蛋白是杜兴氏肌营养不良症（DMD）中存在缺陷的蛋白质产物，存在于所有类型的肌肉和大脑中。尽管30%的DMD患者表现为非进行性智力迟钝，但该蛋白质的功能尚不清楚，其在大脑中的作用也不明确。因此，我们使用针对该蛋白质不同区域产生的抗体，研究了正常和DMD人类胎儿神经元培养物中肌营养不良蛋白的定位。在正常神经元的胞体和轴丘中证实了肌营养不良蛋白免疫反应性，并且似乎与细胞膜的内部相关，尽管也观察到了一些细胞内染色。仅在具有完全发育的神经元特征的细胞中存在阳性肌营养不良蛋白染色，尽管并非所有神经元都是阳性的。神经胶质细胞对该抗原始终呈阴性。用针对脑血影蛋白的抗体进行免疫染色表明，肌营养不良蛋白抗体与这些蛋白质没有交叉反应。讨论了与其他蛋白质交叉反应的可能性。对来自DMD胎儿的培养细胞的研究也显示神经元中存在特异性肌营养不良蛋白免疫染色，尽管肌肉通常对肌营养不良蛋白呈阴性。然而，肌营养不良蛋白免疫染色以及脑血影蛋白和神经丝的定位似乎异常，细胞的整体形态也是如此。这表明肌营养不良蛋白可能在大脑发育过程中起作用，并且肌营养不良蛋白缺乏会导致异常的神经元特征。这与在DMD患者中观察到的智力迟钝的非进行性性质是一致的。
