ArticleJCI insight2019
Cardiac hypertrophy and arrhythmia in mice induced by a mutation in ryanodine receptor 2.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 38 citations in OpenAlex.
- Review
- Prolonged QT Interval in HIV-1 Infected Humanized Mice Treated Chronically with Dolutegravir/Tenofovir Disoproxil Fumarate/Emtricitabine.International journal of molecular sciences · 2026Article
- The clinical and genetic spectrum of pediatric hypertrophic cardiomyopathy manifesting before one year of age.Pediatric research · 2025Article
- Enrichment of mutant calmodulin protein in a murine model of a human calmodulinopathy.JCI insight · 2025Article
- Preventing the phosphorylation of RyR2 at canonical sites reduces CaNature cardiovascular research · 2025Article
- Electrophysiology Models for End-Stage Renal Disease Maladaptations That Promote Asystole.Reviews in cardiovascular medicine · 2025Review
- Experimental Models of Hypertrophic Cardiomyopathy: A Systematic Review.JACC. Basic to translational science · 2025Review
- Early pathological mechanisms in a mouse model of heart failure with preserved ejection fraction.American journal of physiology. Heart and circulatory physiology · 2024Article
- Unveiling the Spectrum of Minor Genes in Cardiomyopathies: A Narrative Review.International journal of molecular sciences · 2024Review
- RyR2 Binding of an Antiarrhythmic Cyclic Depsipeptide Mapped Using Confocal Fluorescence Lifetime Detection of FRET.ACS chemical biology · 2023Article
- Calcium Handling in Inherited Cardiac Diseases: A Focus on Catecholaminergic Polymorphic Ventricular Tachycardia and Hypertrophic Cardiomyopathy.International journal of molecular sciences · 2023Review
- The Role ofCase reports in cardiology · 2023Article
- HumanizedCells · 2022Article
- Review
- Article
- 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
- Therapeutic Approaches of Ryanodine Receptor-Associated Heart Diseases.International journal of molecular sciences · 2022Review
- Ventricular arrhythmia and sudden cardiac death in hypertrophic cardiomyopathy: From bench to bedside.Frontiers in cardiovascular medicine · 2022Review
- Structural Insight Into Ryanodine Receptor Channelopathies.Frontiers in pharmacology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
Abstract
Hypertrophic cardiomyopathy (HCM) is triggered mainly by mutations in genes encoding sarcomeric proteins, but a significant proportion of patients lack a genetic diagnosis. We identified a novel mutation in the ryanodine receptor 2, RyR2-P1124L, in a patient from a genotype-negative HCM cohort. The aim of this study was to determine whether RyR2-P1124L triggers functional and structural alterations in isolated RyR2 channels and whole hearts. We found that P1124L induces significant conformational changes in the SPRY2 domain of RyR2. Recombinant RyR2-P1124L channels displayed a cytosolic loss-of-function phenotype, which contrasted with a higher sensitivity to luminal [Ca2+], indicating a luminal gain-of-function. Homozygous mice for RyR2-P1124L showed mild cardiac hypertrophy, similar to the human patient. This phenotype, evident at 1 yr of age, was accompanied by an increase in the expression of calmodulin (CaM). P1124L mice also showed higher susceptibility to arrhythmia at 8 mo of age, before the onset of hypertrophy. RyR2-P1124L has a distinct cytosolic loss-of-function and a luminal gain-of-function phenotype. This bifunctionally-divergent behavior triggers arrhythmias and structural cardiac remodeling, and involves overexpression of calmodulin as a potential hypertrophic mediator. This study is relevant to continue elucidating the possible causes of genotype-negative HCM and the role of RyR2 in cardiac hypertrophy.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.