The survival motor neuron protein in spinal muscular atrophy
The survival motor neuron protein in spinal muscular atrophy
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DOI：
10.1093/hmg/6.8.1205
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发表时间：
1997-08-01
影响因子：
3.5
通讯作者：
Burghes, AHM
中科院分区：
文献类型：
--
作者：
Coovert, DD;Le, TT;Burghes, AHM
38 kDa存活运动神经元（SMN）蛋白由两个普遍表达的基因编码：端粒SMN （SMNT）和着丝粒SMN （SMNC）。SMNT突变导致近端脊髓性肌萎缩症（SMA），这是一种常染色体隐性遗传病，导致运动神经元的丢失，SMN存在于细胞质和细胞核中。核形式位于称为宝石的结构中。通过一组抗SMN抗体，我们证明SMN蛋白是由SMNT和SMNC基因表达的。对不同临床严重程度的SMA患者的成纤维细胞进行Western blot分析显示，SMN蛋白的数量适度减少，特别是在I型（最严重）患者中。SMA患者成纤维细胞的免疫细胞化学分析表明，I型SMA患者的宝石数量显著减少，宝石数量与临床严重程度相关。这种与表型的相关性使用原代成纤维细胞可以作为一个有用的诊断工具，在一个容易接近的组织。SMN在脑、肾和肝中高水平表达，在骨骼肌和心肌中中等水平表达，在成纤维细胞和淋巴细胞中低水平表达。在SMA患者中，肌肉和淋巴细胞中的SMN水平中度降低。相比之下，SMN在正常人和非sma疾病对照者的脊髓中表达水平较高，但在I型患者的脊髓中表达水平降低了100倍。I型SMA脊髓中SMN的显著减少与这种运动神经元疾病的特征一致。我们认为，I型患者的SMNT破坏导致运动神经元的SMN丢失，导致这些神经元变性。
The 38 kDa survival motor neuron (SMN) protein is encoded by two ubiquitously expressed genes: telomeric SMN (SMNT) and centromeric SMN (SMNC). Mutations in SMNT, but not SMNC, cause proximal spinal muscular atrophy (SMA), an autosomal recessive disorder that results in loss of motor neurons, SMN is found in the cytoplasm and nucleus. The nuclear form is located in structures termed gems. Using a panel of anti-SMN antibodies, we demonstrate that the SMN protein is expressed from both the SMNT and SMNC genes. Western blot analysis of fibroblasts from SMA patients with various clinical severities of SMA showed a moderate reduction in the amount of SMN protein, particularly in type I (most severe) patients. Immunocytochemical analysis of SMA patient fibroblasts indicates a significant reduction in the number of gems in type I SMA patients and a correlation of the number of gems with clinical severity. This correlation to phenotype using primary fibroblasts may serve as a useful diagnostic tool in an easily accessible tissue. SMN is expressed at high levels in brain, kidney and liver, moderate levels in skeletal and cardiac muscle, and low levels in fibroblasts and lymphocytes. In SMA patients, the SMN level was moderately reduced in muscle and lymphoblasts. In contrast, SMN was expressed at high levels in spinal cord from normals and non-SMA disease controls, but was reduced 100-fold in spinal cord from type I patients. The marked reduction of SMN in type I SMA spinal cords is consistent with the features of this motor neuron disease. We suggest that disruption of SMNT in type I patients results in loss of SMN from motor neurons, resulting in the degeneration of these neurons.