Generation of a CRISPR/Cas9-edited Plakoglobin (JUP) knock-out (JMUi001-A-4) iPSC line to model the cardiac phenotype of arrhythmogenic cardiomyopathy

Katharina Walz; Anna Janz; Eva Klopocki; Brenda Gerull

doi:10.1016/j.scr.2023.103240

Generation of a CRISPR/Cas9-edited Plakoglobin (JUP) knock-out (JMUi001-A-4) iPSC line to model the cardiac phenotype of arrhythmogenic cardiomyopathy

Stem Cell Res. 2023 Dec:73:103240. doi: 10.1016/j.scr.2023.103240. Epub 2023 Nov 8.

Authors

Katharina Walz¹, Anna Janz¹, Eva Klopocki², Brenda Gerull³

Affiliations

¹ Comprehensive Heart Failure Center and Medicine I, University Hospital Würzburg, Würzburg, Germany.
² Institute of Human Genetics, Biocenter, University of Würzburg, Würzburg, Germany.
³ Comprehensive Heart Failure Center and Medicine I, University Hospital Würzburg, Würzburg, Germany. Electronic address: [email protected].

PMID: 37995437
DOI: 10.1016/j.scr.2023.103240

Abstract

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.

MeSH terms

Arrhythmogenic Right Ventricular Dysplasia* / genetics
CRISPR-Cas Systems / genetics
Humans
Induced Pluripotent Stem Cells* / metabolism
Myocytes, Cardiac / metabolism
Phenotype
gamma Catenin / genetics
gamma Catenin / metabolism

Substances

gamma Catenin
JUP protein, human