Desmoglein-2 deficiency results in cardiac dysfunction by compromising both Z-disc- and intercalated disc-mediated mechanotransduction.

ABSTRACT: Desmoglein-2 (DSG2), a critical component of the cardiac desmosome and located at the cardiomyocyte-cardiomyocyte intercalated disc, is essential for cell-cell adhesion, cardiomyocyte mechanical stability, and electrical coupling between cells. However, its relative contribution in maintaining cardiac function at the sarcomere level remains unclear. Using 4-week-old (adolescent) and 16-week-old (adult) homozygous knock-in Dsg2-mutant (Dsg2 ^mut/mut) mice, we found that loss of DSG2 leads to early onset chamber- and age-dependent cardiac dysfunction driven by Z-disc structural defects and increased myosin detachment rate. Interestingly, Ca²⁺-activated force was markedly reduced in adolescent Dsg2 ^mut/mut permeabilized left ventricular car

SUBMITTER: Landim-Vieira M 

PROVIDER: S-EPMC12621914 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature