The splicing factor Acin1 is essential for embryonic development but has limited effects on muscle structure and homeostasis.

Apoptotic chromatin condensation inducer 1 (Acin1) is an RNA-binding protein involved in the regulation of alternative splicing, but its physiological function remains unclear. Global deletion of Acin1 causes embryonic lethality around E11.5, with mutants exhibiting developmental delays and increased apoptosis. Using conditional knockout mice, we found that skeletal muscle myofiber-specific Acin1 knockout mice (Acin1 MKO) are viable and fertile and that Acin1 MKO mice show enlarged myofibers and ongoing muscle damage and regeneration, characterized by increased central nuclei and embryonic myosin heavy chain expression. RNA-seq analysis revealed that Acin1 deletion altered the expression and splicing patterns of genes crucial for muscle function. Notable changes included modified splicing of genes associated with muscle disease and mitochondrial function, often resulting in the expression of gene variants typical of immature or diseased muscle. These findings suggest that Acin1 is essential for embryonic development and has limited effects on muscle structure and homeostasis via its regulation of gene expression and alternative splicing.