PDF(Pubmed)
Abstract：
Mutations in skeletal muscle α-actin (Acta1) cause myopathies. In a mouse model of congenital myopathy, heterozygous Acta1 (H40Y) knock-in (Acta1+/Ki) mice exhibit features of human nemaline myopathy, including premature lethality, severe muscle weakness, reduced mobility, and the presence of nemaline rods in muscle fibers. In this study, we investigated the impact of Acta1 (H40Y) mutation on the neuromuscular junction (NMJ). We found that the NMJs were markedly fragmented in Acta1+/Ki mice. Electrophysiological analysis revealed a decrease in amplitude but increase in frequency of miniature end-plate potential (mEPP) at the NMJs in Acta1+/Ki mice, compared with those in wild type (Acta1+/+) mice. Evoked end-plate potential (EPP) remained similar at the NMJs in Acta1+/Ki and Acta1+/+ mice, but quantal content was increased at the NMJs in Acta1+/Ki, compared with Acta1+/+ mice, suggesting a homeostatic compensation at the NMJs in Acta1+/Ki mice to maintain normal levels of neurotransmitter release. Furthermore, short-term synaptic plasticity of the NMJs was compromised in Acta1+/Ki mice. Together, these results demonstrate that skeletal Acta1 H40Y mutation, albeit muscle-origin, leads to both morphological and functional defects at the NMJ.
摘要：
骨骼肌α-肌动蛋白(Acta1)的突变引起肌病。在先天性肌病的小鼠模型中，杂合Acta1（H40Y）敲入（Acta1/Ki）小鼠表现出人线虫肌病的特征，包括过早死亡,严重的肌肉无力,流动性降低，和肌肉纤维中存在线虫棒。在这项研究中,我们研究了Acta1(H40Y)突变对神经肌肉接头(NMJ)的影响.我们发现NMJs在Acta1+/Ki小鼠中明显片段化。电生理分析显示，Acta1/Ki小鼠的NMJ的微型端板电位（mEPP）的振幅降低，但频率增加，与野生型(Acta1+/+)小鼠相比。在Acta1+/Ki和Acta1+/+小鼠的NMJ中,诱发的终板电位(EPP)保持相似,但Acta1+/Ki中NMJ的定量含量增加，与Acta1+/+小鼠相比，提示Acta1/Ki小鼠中NMJ的稳态补偿以维持正常水平的神经递质释放。此外，在Acta1/Ki小鼠中，NMJ的短期突触可塑性受损。一起,这些结果表明骨骼Acta1H40Y突变，尽管肌肉起源，导致NMJ的形态和功能缺陷。
