Knockout of MYOM1 in human cardiomyocytes leads to myocardial atrophy via impairing calcium homeostasis

• DOI: 10.1111/jcmm.16268
• Publication Date: 2021-01-16T06:56:05Z
• Authors: Chengwen Hang; Yuanxiu Song; Ya’nan Li; Siyao Zhang; Yun Chang; Rui Bai; Amina Saleem; Mengqi Jiang; Wenjing Lu; Feng Lan; Ming Cui
• Keywords: Homeostasis; Knockout mouse

Abstract Myomesin‐1 (encoded by MYOM1 gene) is expressed in almost all cross‐striated muscles, whose family (together with myomesin‐2 and myomesin‐3) helps to cross‐link adjacent myosin form the M‐line myofibrils. However, little known about its biological function, causal relationship mechanisms underlying MYOM1‐related myopathies (especially heart). Regrettably, there no MYMO1 knockout model for study so far. A better further understanding of biology urgently needed. Here, we used CRISPR/Cas9 gene‐editing technology establish an human embryonic stem cell line (MYOM1 −/− hESC), which was then differentiated into myomesin‐1 deficient cardiomyocytes hESC‐CMs) vitro. We found that plays important role sarcomere assembly, contractility regulation development. Moreover, myomesin‐1‐deficient hESC‐CMs can recapitulate myocardial atrophy phenotype Based on this model, not only function MYOM1, but also aetiology, pathogenesis, potential treatments caused deficiency be studied.