Spinal muscular atrophy is caused by reduced levels of SMN resulting from the loss of SMN1 and reliance on SMN2 for the production of SMN. Loss of SMN entirely is embryonic lethal in mammals. There are several SMN missense mutations found in humans. These alleles do not show partial function in the absence of wild-type SMN and cannot rescue a null Smn allele in mice. However, these human SMN missense allele transgenes can rescue a null Smn allele when SMN2 is present. We find that the N- and C-terminal regions constitute two independent domains of SMN that can be separated genetically and undergo intragenic complementation. These SMN protein heteromers restore snRNP assembly of Sm proteins onto snRNA and completely rescue both survival of Smn null mice and motor neuron electrophysiology demonstrating that the essential functional unit of SMN is the oligomer.

中文翻译：

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氨基和羧基末端 SMN 错义突变的基因内互补可以拯救 Smn 缺失小鼠


脊髓性肌萎缩症是由于SMN1缺失以及SMN2产生 SMN 的依赖导致 SMN 水平降低所致。 SMN 完全丧失对于哺乳动物来说是胚胎致命的。在人类中发现了几种 SMN 错义突变。这些等位基因在没有野生型 SMN 的情况下不显示部分功能，并且不能挽救小鼠中无效的Smn等位基因。然而，当SMN2存在时，这些人类 SMN 错义等位基因转基因可以挽救无效的Smn等位基因。我们发现SMN的N端和C端区域构成了两个独立的结构域，它们可以在遗传上分开并进行基因内互补。这些 SMN 蛋白异聚体恢复了 Sm 蛋白在 snRNA 上的 snRNP 组装，并完全挽救了Smn无效小鼠的存活和运动神经元电生理学，表明 SMN 的基本功能单位是寡聚体。