The distribution of SMN protein complex in human fetal tissues and its alteration in spinal muscular atrophy
The distribution of SMN protein complex in human fetal tissues and its alteration in spinal muscular atrophy
复制标题
DOI：
10.1093/hmg/7.12.1927
复制
发表时间：
1998-11-01
影响因子：
3.5
通讯作者：
Lefebvre, S
中科院分区：
文献类型：
--
作者：
Burlet, P;Huber, C;Lefebvre, S
脊髓性肌萎缩症（SMA）是一种常见的常染色体隐性遗传性神经肌肉疾病，其特征是脊髓运动神经元变性和肌肉萎缩。 SMA 是由运动神经元存活（SMN）基因的改变引起的，该基因的功能迄今尚不清楚。在这里，我们提出的免疫印迹分析显示，与胎儿发育相比，正常的 SMN 蛋白表达在出生后经历了明显的衰减。人类胎儿组织中 SMN 蛋白的形态学和免疫组织化学分析显示，SMN 蛋白普遍分布在细胞质中，但肌肉细胞除外，其中 SMN 蛋白免疫定位于大的细胞质点状结构，并与无膜重沉降复合物紧密相关。这些细胞质结构的大小与宝石相似。 SMN 蛋白在 I 型 SMA 胎儿的组织中明显缺乏，包括骨骼肌和脊髓（如之前所示）。虽然我们的数据不能帮助确定 SMA 是否是由脊髓、骨骼肌或两者中 SMN 表达受损引起的，但它们表明胚胎-胎儿发育过程中需要 SMN 蛋白。
Spinal muscular atrophy (SMA) is a common autosomal recessive neuromuscular disorder characterized by degeneration of motor neurons of the spinal cord and muscular atrophy. SMA is caused by alterations to the survival of motor neuron (SMN) gene, the function of which has hitherto been unclear. Here, we present immunoblot analyses showing that normal SMN protein expression undergoes a marked decay in the postnatal period compared with fetal development, Morphological and immunohistochemical analyses of the SMN protein in human fetal tissues showed a general distribution in the cytoplasm, except in muscle cells, where SMN protein was immunolocalized to large cytoplasmic dot-like structures and was tightly associated with membrane-free heavy sedimenting complexes. These cytoplasmic structures were similar in size to gem. The SMN protein was markedly deficient in tissues derived from type I SMA fetuses, including skeletal muscles and, as previously shown, spinal cord. While our data do not help decide whether SMA results from impaired SMN expression in spinal cord, skeletal muscle or both, they suggest a requirement for SMN protein during embryo-fetal development.