Walz Katharina, Janz Anna, Klopocki Eva, Gerull Brenda
Comprehensive Heart Failure Center and Medicine I, University Hospital Würzburg, Würzburg, Germany.
Institute of Human Genetics, Biocenter, University of Würzburg, Würzburg, Germany.
Stem Cell Res. 2023 Dec;73:103240. doi: 10.1016/j.scr.2023.103240. Epub 2023 Nov 8.
Arrhythmogenic cardiomyopathy (ACM) represents the cardiac phenotype of Naxos disease, an autosomal recessive disease with an additional cutaneous phenotype. ACM is mainly caused by mutated desmosomal proteins, which are part of cardiac adherens junctions and provide mechanical and electrical stability. Here, we generated a knock-out (KO) of the junctional protein Plakoglobin (JUP-KO; JMUi001-A-4) using the CRISPR/Cas9 system in healthy control induced pluripotent stem cells (iPSCs, (JMUi001-A). JUP-KO iPSCs maintained pluripotency, differentiation potential and genomic integrity and provide an in vitro system modelling ACM when differentiated into cardiomyocytes.
致心律失常性心肌病（ACM）是纳克索斯病的心脏表型，纳克索斯病是一种常染色体隐性疾病，还伴有皮肤表型。ACM主要由桥粒蛋白突变引起，桥粒蛋白是心脏黏附连接的一部分，可提供机械和电稳定性。在此，我们使用CRISPR/Cas9系统在健康对照诱导多能干细胞（iPSCs，(JMUi001-A)）中敲除连接蛋白盘状球蛋白（JUP-KO；JMUi001-A-4）。JUP-KO iPSCs保持了多能性、分化潜能和基因组完整性，并在分化为心肌细胞时提供了一个模拟ACM的体外系统。
