ArticleCirculation. Arrhythmia and electrophysiology2015
Mouse Model of Human Congenital Heart Disease: Progressive Atrioventricular Block Induced by a Heterozygous Nkx2-5 Homeodomain Missense Mutation.
Article in Circulation. Arrhythmia and electrophysiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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
21 citing papers in PubMed, 30 citations in OpenAlex.
- Models of the human heart for biomedical research: Opportunities and challenges.Physiological reports · 2026Review
- Multimodal optical coherence tomography and two-photon light sheet fluorescence microscopy for embryo imaging.Journal of biomedical optics · 2025Article
- Sudden Death in Pediatric Patient With Dilated Cardiomyopathy Due to Founder Variant inAcademic forensic pathology · 2024Article
- New drug discovery of cardiac anti-arrhythmic drugs: insights in animal models.Scientific reports · 2023Article
- Linagliptin and secoisolariciresinol diglucoside attenuate hyperlipidemia and cardiac hypertrophy induced by a high-methionine diet in rats via suppression of hyperhomocysteinemia-induced endoplasmic reticulum stress.Frontiers in pharmacology · 2023Article
- Animal Models to Study Cardiac Arrhythmias.Circulation research · 2022Review
- A NovelJournal of clinical medicine · 2022Article
- Association between single-nucleotide polymorphisms ofOpen life sciences · 2022Article
- Genetics of congenital heart disease: a narrative review of recent advances and clinical implications.Translational pediatrics · 2021Review
- New Insights into the Development and Morphogenesis of the Cardiac Purkinje Fiber Network: Linking Architecture and Function.Journal of cardiovascular development and disease · 2021Review
- Personalized Genetic Diagnosis of Congenital Heart Defects in Newborns.Journal of personalized medicine · 2021Review
- In Vivo and In Vitro Genetic Models of Congenital Heart Disease.Cold Spring Harbor perspectives in biology · 2021Review
- Atrial and Sinoatrial Node Development in the Zebrafish Heart.Journal of cardiovascular development and disease · 2021Review
- Experimental Rodent Models of Cardiovascular Diseases.Frontiers in cardiovascular medicine · 2020Review
- Metformin intervention prevents cardiac dysfunction in a murine model of adult congenital heart disease.Molecular metabolism · 2019Article
- Furin, a transcriptional target of NKX2-5, has an essential role in heart development and function.PloS one · 2019Article
- Genetic Basis for Congenital Heart Disease: Revisited: A Scientific Statement From the American Heart Association.Circulation · 2018Review
- Systems Genetics Approaches in Rat Identify Novel Genes and Gene Networks Associated With Cardiac Conduction.Journal of the American Heart Association · 2018Article
- NKX2-5 regulates human cardiomyogenesis via a HEY2 dependent transcriptional network.Nature communications · 2018Article
- Mechanism Sharing Between Genetic and Gestational Hypoxia-Induced Cardiac Anomalies.Frontiers in cardiovascular medicine · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundHeterozygous human NKX2-5 homeodomain (DNA-binding domain) missense mutations are highly penetrant for varied congenital heart defects, including progressive atrioventricular (AV) block requiring pacemaker implantation. We recently replicated this genetic defect in a murine knockin model, in which we demonstrated highly penetrant, pleiotropic cardiac anomalies. In this study, we examined postnatal AV conduction in the knockin mice. METHODS AND
resultsA murine knockin model (Arg52Gly, Nkx2-5(+/R52G)) in a 129/Sv background was analyzed by histopathology, surface, and telemetry ECG, and in vivo electrophysiology studies, comparing with control Nkx2-5(+/+) mice at diverse postnatal stages, ranging from postnatal day 1 (P1) to 17 months. PR prolongation (first degree AV block) was present at 4 weeks, 7 months, and 17 months of age, but not at P1 in the mutant mice. Advanced AV block was also occasionally demonstrated in the mutant mice. Electrophysiology studies showed that AV nodal function and right ventricular effective refractory period were impaired in the mutant mice, whereas sinus nodal function was not affected. AV nodal size was significantly smaller in the mutant mice than their controls at 4 weeks of age, corresponding to the presence of PR prolongation, but not P1, suggesting, at least in part, that the conduction abnormalities are the result of a morphologically atrophic AV node.
conclusionsThe highly penetrant and progressive AV block phenotype seen in human heterozygous missense mutations in NKX2-5 homeodomain was replicated in mice by knocking in a comparable missense mutation.
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.