MYH6 encodes the alpha heavy chain subunit of cardiac myosin. Mutations in MYH6 cause cardiomyopathy and congenital heart defects. However, due to embryonic lethality in MYH6 knockout mice, the precise roles of MYH6 in cardiomyopathy, congenital heart defects and development process remain largely unknown. In this study, we generated a human MYH6 compound heterozygous knockout hESC line using CRISPR/Cas9 technology. The establishment cell line WAe009-A-46 carried a compound heterozygous 2 bp deletion/7 bp deletion in MYH6, expressed pluripotency markers, showed a normal karyotype and exhibited capability to differentiate into the three germ layers in vitro. MYH6 protein was not detectable in WAe009-A-46 line. This cell line provides a useful tool for studying the role of MYH6 in cardiomyopathy and congenital heart defects.

MYH6编码心肌肌球蛋白的α重链亚基。 MYH6突变会导致心肌病和先天性心脏缺陷。然而，由于MYH6敲除小鼠的胚胎致死性， MYH6在心肌病、先天性心脏缺陷和发育过程中的确切作用仍然很大程度上未知。在本研究中，我们利用CRISPR/Cas9技术构建了人类MYH6复合杂合敲除hESC系。建立的细胞系WAe009-A-46在MYH6中携带复合杂合2 bp缺失/7 bp缺失，表达多能性标记，显示正常核型并表现出体外分化为三个胚层的能力。在 WAe009-A-46 系中未检测到MYH6蛋白。该细胞系为研究 MYH6 在心肌病和先天性心脏缺陷中的作用提供了有用的工具。