ArticlePloS one2014
Generation and characterization of a mouse model harboring the exon-3 deletion in the cardiac ryanodine receptor.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- Long-term efficacy and safety of cardiac genome editing for catecholaminergic polymorphic ventricular tachycardia.The journal of cardiovascular aging · 2024Article
- RYR2 deficient human model identifies calcium handling and metabolic dysfunction impacting pharmacological responses.Frontiers in cardiovascular medicine · 2024Article
- New drug discovery of cardiac anti-arrhythmic drugs: insights in animal models.Scientific reports · 2023Article
- Optical Mapping of Cardiomyocytes in Monolayer Derived from Induced Pluripotent Stem Cells.Cells · 2023Review
- Animal Models to Study Cardiac Arrhythmias.Circulation research · 2022Review
- Preserved cardiac performance and adrenergic response in a rabbit model with decreased ryanodine receptor 2 expression.Journal of molecular and cellular cardiology · 2022Article
- TRIC-A regulates intracellular CaPflugers Archiv : European journal of physiology · 2021Review
- Article
- A Multi-Omics Approach Using a Mouse Model of Cardiac Malformations for Prioritization of Human Congenital Heart Disease Contributing Genes.Frontiers in cardiovascular medicine · 2021Article
- Article
- Gene therapy for inherited arrhythmias.Cardiovascular research · 2020Review
- Identification of a Novel Homozygous Multi-Exon Duplication in RYR2 Among Children With Exertion-Related Unexplained Sudden Deaths in the Amish Community.JAMA cardiology · 2020Article
- TRIC-A Channel Maintains Store Calcium Handling by Interacting With Type 2 Ryanodine Receptor in Cardiac Muscle.Circulation research · 2020Article
- IP3R-Mediated Compensatory Mechanism for Calcium Handling in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes With Cardiac Ryanodine Receptor Deficiency.Frontiers in cell and developmental biology · 2020Article
- Genetic Testing for Inherited Cardiac Arrhythmias: Current State-of-the-Art and Future Avenues.The Journal of innovations in cardiac rhythm management · 2018Review
- An optogenetic arrhythmia model to study catecholaminergic polymorphic ventricular tachycardia mutations.Scientific reports · 2017Article
- Cardiac disease and arrhythmogenesis: Mechanistic insights from mouse models.International journal of cardiology. Heart & vasculature · 2016Review
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
A large genomic deletion in human cardiac ryanodine receptor (RYR2) gene has been detected in a number of unrelated families with various clinical phenotypes, including catecholaminergic polymorphic ventricular tachycardia (CPVT). This genomic deletion results in an in-frame deletion of exon-3 (Ex3-del). To understand the underlying disease mechanism of the RyR2 Ex3-del mutation, we generated a mouse model in which the RyR2 exon-3 sequence plus 15-bp intron sequences flanking exon-3 were deleted. Heterozygous Ex3-del mice (Ex3-del+/-) survived, but no homozygous Ex3-del mice were born. Unexpectedly, the Ex3-del+/- mice are not susceptible to CPVT. Ex3-del+/- cardiomyocytes exhibited similar amplitude but altered dynamics of depolarization-induced Ca2+ transients compared to wild type (WT) cells. Immunoblotting analysis revealed markedly reduced expression of RyR2 protein in the Ex3-del+/- mutant heart, indicating that Ex3-del has a major impact on RyR2 protein expression in mice. Cardiac specific, conditional knockout of the WT RyR2 allele in Ex3-del+/- mice led to bradycardia and death. Thus, the absence of CPVT and other phenotypes in Ex3-del+/- mice may be attributable to the predominant expression of the WT RyR2 allele as a result of the markedly reduced expression of the Ex3-del mutant allele. The effect of Ex3-del on RyR2 protein expression is discussed in relation to the phenotypic variability in individuals with the RyR2 exon-3 deletion.
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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.