ArticleThe Journal of clinical investigation2015
Genetically engineered SCN5A mutant pig hearts exhibit conduction defects and arrhythmias.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 110 citations in OpenAlex.
- From farm to lab: gene-edited sheep transforming bone research.JBMR plus · 2026Review
- Advances in Conductive Nanomaterials for Cardiac Arrhythmia and Future Directions in Bioevaluation Strategies.Advanced healthcare materials · 2025Review
- SCN10A-short gene therapy to restore conduction and protect against malignant cardiac arrhythmias.European heart journal · 2025Article
- The pig as an optimal animal model for cardiovascular research.Lab animal · 2024Review
- Popeye domain containing proteins modulate the voltage-gated cardiac sodium channel Nav1.5.iScience · 2024Article
- Brugada Syndrome: A Comprehensive Review of Fundamental and Electrophysiological New Findings.Journal of clinical medicine · 2023Review
- New drug discovery of cardiac anti-arrhythmic drugs: insights in animal models.Scientific reports · 2023Article
- A novel porcine model of CLN3 Batten disease recapitulates clinical phenotypes.Disease models & mechanisms · 2023Article
- Mouse models of spontaneous atrial fibrillation.Mammalian genome : official journal of the International Mammalian Genome Society · 2023Review
- Subepicardial Cardiomyopathy: A Disease Underlying J-Wave Syndromes and Idiopathic Ventricular Fibrillation.Circulation · 2023Article
- Automated Patch-Clamp and Induced Pluripotent Stem Cell-Derived Cardiomyocytes: A Synergistic Approach in the Study of Brugada Syndrome.International journal of molecular sciences · 2023Review
- Genetic Profile and Clinical Characteristics of Brugada Syndrome in the Chinese Population.Journal of cardiovascular development and disease · 2022Article
- Brugada Syndrome Associated with Different HeterozygousJournal of clinical medicine · 2022Article
- J wave syndromes: What's new?Trends in cardiovascular medicine · 2022Review
- Animal Models to Study Cardiac Arrhythmias.Circulation research · 2022Review
- Brugada Syndrome: Different Experimental Models and the Role of Human Cardiomyocytes From Induced Pluripotent Stem Cells.Journal of the American Heart Association · 2022Review
- A practical guide to setting up pig models for cardiovascular catheterization, electrophysiological assessment and heart disease research.Lab animal · 2022Review
- Cardiac Macrophages and Their Effects on Arrhythmogenesis.Frontiers in physiology · 2022Review
- AInternational journal of molecular sciences · 2021Article
- Review
3 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
SCN5A encodes the α subunit of the major cardiac sodium channel Na(V)1.5. Mutations in SCN5A are associated with conduction disease and ventricular fibrillation (VF); however, the mechanisms that link loss of sodium channel function to arrhythmic instability remain unresolved. Here, we generated a large-animal model of a human cardiac sodium channelopathy in pigs, which have cardiac structure and function similar to humans, to better define the arrhythmic substrate. We introduced a nonsense mutation originally identified in a child with Brugada syndrome into the orthologous position (E558X) in the pig SCN5A gene. SCN5A(E558X/+) pigs exhibited conduction abnormalities in the absence of cardiac structural defects. Sudden cardiac death was not observed in young pigs; however, Langendorff-perfused SCN5A(E558X/+) hearts had an increased propensity for pacing-induced or spontaneous VF initiated by short-coupled ventricular premature beats. Optical mapping during VF showed that activity often began as an organized focal source or broad wavefront on the right ventricular (RV) free wall. Together, the results from this study demonstrate that the SCN5A(E558X/+) pig model accurately phenocopies many aspects of human cardiac sodium channelopathy, including conduction slowing and increased susceptibility to ventricular arrhythmias.
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