ArticleHuman molecular genetics2014
Connexin defects underlie arrhythmogenic right ventricular cardiomyopathy in a novel mouse model.
Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.
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Who cites it
69 citing papers in PubMed, 1 synthesis or guideline pooled it, 111 citations in OpenAlex.
- Facts and Gaps in Exercise Influence on Arrhythmogenic Cardiomyopathy: New Insights From a Meta-Analysis Approach.Frontiers in cardiovascular medicine · 2021Pooled it
- PKP2 orchestrates OXPHOS expression in cardiomyocytes via a PGC1α-dependent mechanism.Cardiovascular research · 2026Article
- Desmoplakin Loss Leads to PKC- and Src-Mediated Contractile Dysfunction in Cardiomyocytes.Circulation research · 2026Article
- Zebrafish dspb-/- mutant as a model for non-dilated left ventricular cardiomyopathy: exploring cardiac dysfunction and exercise modulation.Molecular biomedicine · 2026Article
- RhoGEF Ect2 supports RhoA activity at cell-cell junctions through desmoplakin.Life science alliance · 2026Article
- Connexin-43 Restoration Alleviates Desmosomal Arrhythmogenic Cardiomyopathy.Circulation. Heart failure · 2026Article
- Molecular Pathogenesis of Arrhythmogenic Cardiomyopathy: Mechanisms and Therapeutic Perspectives.Biomolecules · 2025Review
- Desmoglein-2 deficiency results in cardiac dysfunction by compromising both Z-disc- and intercalated disc-mediated mechanotransduction.bioRxiv : the preprint server for biology · 2025Article
- Exercise Prescription in Arrhythmogenic Cardiomyopathy: Finding the Right Balance Between Risks and Benefits.Journal of the American Heart Association · 2025Review
- Article
- Cardiac sympathetic neurons are additional cells affected in genetically determined arrhythmogenic cardiomyopathy.The Journal of physiology · 2025Article
- Desmoplakin Cardiomyopathy: Role of Inflammation and Potential Role of Disease-Modifying Therapies.Current cardiology reports · 2025Review
- Machine learning analysis of ARVC informed by sodium channel protein-based interactome networks.Frontiers in pharmacology · 2025Article
- In Vivo Approaches to Understand Arrhythmogenic Cardiomyopathy: Perspectives on Animal Models.Cells · 2024Review
- Animal Models and Molecular Pathogenesis of Arrhythmogenic Cardiomyopathy Associated with Pathogenic Variants in Intercalated Disc Genes.International journal of molecular sciences · 2024Review
- Article
- Molecular Pathways and Animal Models of Arrhythmias.Advances in experimental medicine and biology · 2024Article
- Plakophilin 2 gene therapy prevents and rescues arrhythmogenic right ventricular cardiomyopathy in a mouse model harboring patient genetics.Nature cardiovascular research · 2023Article
- Arrhythmogenic Cardiomyopathy: from Preclinical Models to Genotype-phenotype Correlation and Pathophysiology.Stem cell reviews and reports · 2023Review
- Chronic diastolic stretch unmasks conduction defects in an in vitro model of arrhythmogenic cardiomyopathy.American journal of physiology. Heart and circulatory physiology · 2023Article
9 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 2 institutions in 2 countries.
Funding
Abstract
Arrhythmogenic right ventricular cardiomyopathy (ARVC) termed a 'disease of the desmosome' is an inherited cardiomyopathy that recently underwent reclassification owing to the identification of left-dominant and biventricular disease forms. Homozygous loss-of-function mutations in the desmosomal component, desmoplakin, are found in patients exhibiting a biventricular form of ARVC; however, no models recapitulate the postnatal hallmarks of the disease as seen in these patients. To gain insights into the homozygous loss-of-function effects of desmoplakin in the heart, we generated cardiomyocyte-specific desmoplakin-deficient mice (DSP-cKO) using ventricular myosin light chain-2-Cre mice. Homozygous DSP-cKO mice are viable but display early ultrastructural defects in desmosomal integrity leading to a cardiomyopathy reminiscent of a biventricular form of ARVC, which includes cell death and fibro-fatty replacement within the ventricle leading to biventricular dysfunction, failure and premature death. DSP-cKO mice also exhibited ventricular arrhythmias that are exacerbated with exercise and catecholamine stimulation. Furthermore, DSP-cKO hearts exhibited right ventricular conduction defects associated with loss of connexin 40 expression and electrical wavefront propagation defects associated with loss of connexin 43 expression. Dose-dependent assessment of the effects of loss of desmoplakin in neonatal ventricular cardiomyocytes revealed primary loss of connexin 43 levels, phosphorylation and function independent of the molecular dissociation of the mechanical junction complex and fibro-fatty manifestation associated with ARVC, suggesting a role for desmoplakin as a primary stabilizer of connexin integrity. In summary, we provide evidence for a novel mouse model, which is reminiscent of the postnatal onset of ARVC while highlighting mechanisms underlying a biventricular form of human ARVC.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.