Loss of plakoglobin immunoreactivity in intercalated discs in arrhythmogenic right ventricular cardiomyopathy: protein mislocalization versus epitope masking

To examine the relevance and cause of reduced plakoglobin IF in intercalated discs for arrhythmogenic right ventricular cardiomyopathy (ARVC) and ARVC-like disease in mouse and human. Normalized semi-quantitative IF measurements were performed in a standardized format in desmoglein 2-mutant mice with an ARVC-like phenotype (n = 6) and in cardiac biopsies from humans with ARVC and non-ARVC heart disease (n = 10). Reduced plakoglobin staining was detectable in ARVC only with one antibody directed against a defined epitope but not with three other antibodies reacting with different epitopes of plakoglobin. Reduced plakoglobin staining in intercalated discs of heart tissue from human ARVC patients and in a murine ARVC model is caused by alterations in epitope accessibility and not by protein relocalization.