Battaglia G, Princivalle A, Forti F, Lizier C, Zeviani M
Department of Neurophysiology, Istituto Neurologico C. Besta, Milano, Italy.
Hum Mol Genet. 1997 Oct;6(11):1961-71. doi: 10.1093/hmg/6.11.1961.
The survival motor neuron (SMN) gene is the putative disease gene for human spinal muscular atrophy (SMA), an autosomal recessive disorder characterized by progressive degeneration of lower motor neurons. Two copies of the gene, centromeric and telomeric, are present in the same 5q13 chromosomal region in humans. However, only the telomeric gene is affected in SMA. The SMN gene(s) encode(s) a novel protein of unknown function. To gain insights into the role of SMN in neurons, we have identified the SMN gene ortholog in the rat, and investigated SMN expression in the CNS of rat, monkey and humans by immunocytochemistry and in situ hybridization experiments. Antibodies against the SMN amino-terminus specifically recognized a single protein identical to the in vitro translation products of human and rat SMN cDNAs. The SMN gene transcript and product were widely but unevenly expressed throughout cerebral and spinal cord areas. The SMN protein was localized mainly in the cytoplasm of specific neuronal systems, and it was particularly expressed in lower motor neurons of newborn and adult animals. Likewise, a strong hybridization signal was detected in lamina IX of the spinal ventral horn. These results support the relevance of SMN for the motor neuron function and the pathogenetic role of the SMN gene in the neuronal degeneration associated with SMA.
生存运动神经元（SMN）基因是人类脊髓性肌萎缩症（SMA）的假定致病基因，这是一种常染色体隐性疾病，其特征为下运动神经元进行性退化。该基因有两个拷贝，着丝粒型和端粒型，位于人类5q13染色体的同一区域。然而，在SMA中只有端粒基因受到影响。SMN基因编码一种功能未知的新型蛋白质。为深入了解SMN在神经元中的作用，我们在大鼠中鉴定出了SMN基因的直系同源基因，并通过免疫细胞化学和原位杂交实验研究了大鼠、猴子和人类中枢神经系统中SMN的表达情况。针对SMN氨基末端的抗体特异性识别出一种单一蛋白质，该蛋白质与人类和大鼠SMN cDNA的体外翻译产物相同。SMN基因转录本和产物在整个脑和脊髓区域广泛但不均匀地表达。SMN蛋白主要定位于特定神经元系统的细胞质中，在新生和成年动物的下运动神经元中尤其表达。同样，在脊髓腹角的IX层检测到强烈的杂交信号。这些结果支持了SMN与运动神经元功能的相关性以及SMN基因在与SMA相关的神经元退化中的致病作用。
