ArticleScientific reports2020
Translating GWAS-identified loci for cardiac rhythm and rate using an in vivo image- and CRISPR/Cas9-based approach.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.
- Genetic insights into resting heart rate and its role in cardiovascular disease.Nature communications · 2023Pooled it
- Current status and challenges of multi-omics research using animal models of atherosclerosis.Journal of molecular and cellular cardiology plus · 2025Review
- Rapid and robust generation of cardiomyocyte-specific crispants in zebrafish using the cardiodeleter system.Cell reports methods · 2025Article
- Functionally characterizing obesity-susceptibility genes using CRISPR/Cas9, in vivo imaging and deep learning.Scientific reports · 2025Article
- G protein regulation by RGS proteins in the pathophysiology of dilated cardiomyopathy.American journal of physiology. Heart and circulatory physiology · 2025Review
- Zebrafish Congenital Heart Disease Models: Opportunities and Challenges.International journal of molecular sciences · 2024Review
- Regulation of heart rate following genetic deletion of the ß1 adrenergic receptor in larval zebrafish.Acta physiologica (Oxford, England) · 2022Article
- CRISPR-Cas9 induces large structural variants at on-target and off-target sites in vivo that segregate across generations.Nature communications · 2022Article
- Modeling Human Cardiac Arrhythmias: Insights from Zebrafish.Journal of cardiovascular development and disease · 2022Review
- Two HCN4 Channels Play Functional Roles in the Zebrafish Heart.Frontiers in physiology · 2022Article
- Drivers of Sinoatrial Node Automaticity in Zebrafish: Comparison With Mechanisms of Mammalian Pacemaker Function.Frontiers in physiology · 2022Article
- Expression Profile of New Marker Genes Involved in Differentiation of Canine Adipose-Derived Stem Cells into Osteoblasts.International journal of molecular sciences · 2021Article
- In vivo identification and validation of novel potential predictors for human cardiovascular diseases.PloS one · 2021Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 4 countries.
Funding
Abstract
A meta-analysis of genome-wide association studies (GWAS) identified eight loci that are associated with heart rate variability (HRV), but candidate genes in these loci remain uncharacterized. We developed an image- and CRISPR/Cas9-based pipeline to systematically characterize candidate genes for HRV in live zebrafish embryos. Nine zebrafish orthologues of six human candidate genes were targeted simultaneously in eggs from fish that transgenically express GFP on smooth muscle cells (Tg[acta2:GFP]), to visualize the beating heart. An automated analysis of repeated 30 s recordings of beating atria in 381 live, intact zebrafish embryos at 2 and 5 days post-fertilization highlighted genes that influence HRV (hcn4 and si:dkey-65j6.2 [KIAA1755]); heart rate (rgs6 and hcn4); and the risk of sinoatrial pauses and arrests (hcn4). Exposure to 10 or 25 µM ivabradine-an open channel blocker of HCNs-for 24 h resulted in a dose-dependent higher HRV and lower heart rate at 5 days post-fertilization. Hence, our screen confirmed the role of established genes for heart rate and rhythm (RGS6 and HCN4); showed that ivabradine reduces heart rate and increases HRV in zebrafish embryos, as it does in humans; and highlighted a novel gene that plays a role in HRV (KIAA1755).
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