Department of Doppler Ultrasonic, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Department of Cardiology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Stem Cell Res. 2021 Oct;56:102562. doi: 10.1016/j.scr.2021.102562. Epub 2021 Oct 7.
The FLNC gene encodes the sarcomeric protein filamin C which plays a central role in cardiomyocytes. Truncating FLNC mutations (stop or frameshift etc.) also cause dilated cardiomyopathy (DCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC). To further understand the exact role of FLNC in DCM, we have generated a human FLNC knockout cell line from the original embryonic stem cell line H9 by CRISPR/Cas9 gene editing technology in this study. The establishment cell line WAe009-A-70 have a compound heterozygous 4 bp deletion/13 bp deletion in the exon 1 of FLNC which resulted in a frameshift in the translation of FLNC. No filamin C protein was detected in cardiomyocytes differentiated from this cell line. Moreover, WAe009-A-70 also expressed pluripotency markers, maintained the ability to differentiate into the three germ layers in vitro and had a normal karyotype.
FLNC 基因编码的肌节蛋白 filamin C 在心肌细胞中起着核心作用。截断的 FLNC 突变（终止或移码等）也会导致扩张型心肌病（DCM）和致心律失常性右室心肌病（ARVC）。为了进一步了解 FLNC 在 DCM 中的确切作用，我们使用 CRISPR/Cas9 基因编辑技术从原始胚胎干细胞系 H9 中生成了人类 FLNC 敲除细胞系。该细胞系 WAe009-A-70 在 FLNC 的外显子 1 中存在 4 个碱基对缺失/13 个碱基对缺失的复合杂合突变，导致 FLNC 翻译发生移码。从该细胞系分化而来的心肌细胞中未检测到 filamin C 蛋白。此外，WAe009-A-70 还表达多能性标记物，保持体外向三个胚层分化的能力，且具有正常的核型。
