Nuclear targeting defect of SMN lacking the C-terminus in a mouse model of spinal muscular atrophy
Nuclear targeting defect of SMN lacking the C-terminus in a mouse model of spinal muscular atrophy
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DOI：
10.1093/hmg/9.5.849
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发表时间：
2000-03-22
影响因子：
3.5
通讯作者：
Melki, J
中科院分区：
文献类型：
--
作者：
Frugier, T;Tiziano, FD;Melki, J
运动神经元基因(SMN)外显子7是在脊髓性肌萎缩症(SMA)患者中发现的最常见的突变，其缺失使得能够产生SMA的小鼠模型，从而证明该基因缺陷是运动神经元的主要靶点。此外，突变的SMN蛋白(SMN Delta C15)在运动神经元细胞核中显著减少，导致缺乏与卷曲身体特异性蛋白Colin的大聚集相关的宝石。这些结果表明，SMN缺乏核靶向性是SMA的生化缺陷。
Deletion of the murine survival of motor neuron gene (SMN) exon 7, the most frequent mutation found in spinal muscular atrophy (SMA) patients, directed to neurons but not to skeletal muscle, enabled generation of a mouse model of SMA providing evidence that motor neurons are the primary target of the gene defect Moreover, the mutated SMN protein (SMN Delta C15) is dramatically reduced in the motor neuron nuclei and causes a lack of gems associated with large aggregates of coilin, a coiled-body-specific protein. These results identify the lack of the nuclear targeting of SMN as the biochemical defect in SMA.