Slow-twitch skeletal muscle defects accompany cardiac dysfunction in transgenic mice with a mutation in the myosin regulatory light chain

What is it about?

In this report, we studied transgenic mice expressing a hypertrophic cardiomyopathy (HCM) mutation (p. Arg58-to-Gln) in the MYL2 gene encoding the human ventricular and slow-twitch skeletal isoforms of myosin regulatory light chain (RLC). We showed that even though R58Q expression was restricted to the heart of mice, functional similarities were clearly observed between the hearts and slow-twitch skeletal muscle. The HCM-mediated adverse heart remodeling in transgenic R58Q mice was echoed in soleus muscle of mice as observed in contractile force measurements, small-angle X-ray diffraction study and by quantitative proteomics. Differential expression of proteins involved in energy metabolism, cell-cell interactions and protein-protein signaling were concurrently observed in the hearts and soleus muscles of R58Q mice. Interestingly, combined involvement of cardiac and soleus muscles in the manifestation of mutation-induced defects bore relevance to the previously described phenotype associated with MYL2 mutations responsible for cardiac and slow-twitch skeletal muscle pathophysiology, leading to cardioskeletal myopathy in patients. Our multi-level investigation suggested that RLC animal models of HCM, just like transgenic R58Q mice, may be considered as useful research tools to study the molecular, energetic and cellular mechanisms of a dual cardioskeletal myopathy associated with the MYL2 gene.

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