Progressive Reduction in Right Ventricular Contractile Function Attributable to Altered Actin Expression in an Aging Mouse Model of Arrhythmogenic Cardiomyopathy.

ABSTRACT:

Background

Arrhythmogenic cardiomyopathy (ACM) is an inherited genetic disorder of desmosomal dysfunction, and PKP2 (plakophilin-2) has been reported to be the most common disease-causing gene when mutation-positive. In the early concealed phase, the ACM heart is at high risk of sudden cardiac death before cardiac remodeling occurs because of mistargeted ion channels and altered Ca²⁺ handling. However, the results of pathogenic PKP2 variants on myocyte contraction in ACM pathogenesis remain unknown.

Methods

We studied the outcomes of a human truncating variant of PKP2 on myocyte contraction using a novel knock-in mouse model with insertion of thymidine in exon 5 of Pkp2, which mimics a familial case of ACM (PKP2-L404fsX5). We used serial echocardiography, e

SUBMITTER: Camors EM 

PROVIDER: S-EPMC9133220 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature