Pena S D, Opas M, Turksen K, Kalnins V I, Carpenter S
Eur J Cell Biol. 1983 Sep;31(2):227-34.
Giant axonal neuropathy (GAN) is a severe autosomal recessive disease affecting both the peripheral and central nervous systems. It is characterized by segmental axonal ballooning due to large neurofilamentous masses and abnormal aggregation of filaments in other cell types including glial cells. Coomassie blue staining of the detergent-resistant cytoskeleton of cultured skin fibroblasts from three patients with GAN revealed the presence of large cytoplasmic filamentous aggregates in the great majority of cells. The aggregates were birefringent when viewed under polarization microscopy and electron microscopy showed that they were composed of aggregates of 8 to 10 nm intermediate filaments. The aggregates stained with antisera specific for vimentin but did not stain with antibodies to actin, tubulin, or the high molecular weight (HMW) microtubule associated protein. Examination of the fibroblasts containing the vimentin aggregates with antibodies to tubulin and the HMW protein showed that they had a normal distribution of microtubules and that the microtubules present were normally associated with the HMW protein. The results suggest that giant axonal neuropathy is a generalized inborn error of organization of intermediate filaments and that a defect in microtubules or their association with HMW protein is not responsible for the observed aggregation of intermediate filaments in this disease. Further study of GAN may be useful in understanding the function of intermediate filaments.
巨轴索神经病（GAN）是一种严重的常染色体隐性疾病，会影响外周和中枢神经系统。其特征是由于大量神经丝团块以及包括神经胶质细胞在内的其他细胞类型中细丝的异常聚集导致节段性轴突肿胀。对三名GAN患者培养的皮肤成纤维细胞的抗去污剂细胞骨架进行考马斯亮蓝染色，结果显示绝大多数细胞中存在大量细胞质丝状聚集体。在偏振显微镜下观察时，这些聚集体具有双折射性，电子显微镜显示它们由8至10纳米中间丝的聚集体组成。这些聚集体用波形蛋白特异性抗血清染色，但不用肌动蛋白、微管蛋白或高分子量（HMW）微管相关蛋白的抗体染色。用微管蛋白和HMW蛋白抗体检查含有波形蛋白聚集体的成纤维细胞，结果显示它们的微管分布正常，且存在的微管与HMW蛋白正常相关。结果表明，巨轴索神经病是中间丝组织的一种全身性先天性缺陷，并且微管或其与HMW蛋白的关联缺陷并非导致该疾病中观察到的中间丝聚集的原因。对GAN的进一步研究可能有助于理解中间丝的功能。
