Myh1, encoding a major adult muscle fiber protein, is crucial for muscle-related functions. It is associated with muscle fiber types, as it is expressed in type IIX fibers in adult rodent skeletal muscles [5]. The gene is likely involved in pathways related to muscle contraction and development. Genetic models, such as gene-knockout mouse models, can provide insights into its in-vivo functions.

In Myh1-knockout mice, there is a disruption of outer hair cell (OHC) electromotility, leading to hearing loss. The prestin activity in OHCs was lower in these knockout mice compared to wild-type mice. Whole-exome sequencing of 437 patients with unexplained hearing loss identified biallelic missense variants of MYH1 in five families. The hearing loss in these individuals was non-progressive, with onset from congenital to childhood, and some also had osteopenia. Structural and functional analyses of the identified variants showed abnormalities and loss of MYH1 functions [1]. In humans, a patient with recurrent rhabdomyolysis was found to have a novel missense variant in MYH1. In horses, the E321G MYH1 mutation is strongly associated with non-exertional rhabdomyolysis and immune-mediated myositis, and in Quarter Horses, it leads to myofibre hyper-contractility [2,3,4,6].

In conclusion, Myh1 is essential for normal muscle function, as demonstrated in gene-knockout models. Its role in muscle-related diseases, such as hearing loss and rhabdomyolysis, has been revealed through research on these models. Understanding Myh1's functions can contribute to better understanding of the pathogenesis of these diseases and potentially lead to new therapeutic strategies.