Key result
Heterozygous Acta1 (H40Y) knock-in mutation in mice led to marked fragmentation of neuromuscular junctions and compromised short-term synaptic plasticity compared to wild-type mice.
Why the study?
Mutations in skeletal muscle α-actin cause myopathies, but the impact of the Acta1 (H40Y) mutation on the neuromuscular junction was unknown.
The skeletal Acta1 H40Y mutation leads to both morphological and functional defects at the neuromuscular junction in a mouse model of congenital myopathy.
May implicate NMJ defects in congenital myopathy; leaves open human translation.
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.
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Liu et al. (2023) studied ACTA1 congenital myopathy. Heterozygous Acta1 (H40Y) knock-in mutation (Acta1+/Ki) vs. Wild type (Acta1+/+) mice was evaluated on Morphological and functional defects at the neuromuscular junction. Heterozygous Acta1 (H40Y) knock-in mutation in mice led to marked fragmentation of neuromuscular junctions and compromised short-term synaptic plasticity compared to wild-type mice.
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