ArticleThe Journal of clinical investigation2001
Progressive atrioventricular conduction defects and heart failure in mice expressing a mutant Csx/Nkx2.5 homeoprotein.
Article in The Journal of clinical investigation, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 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
47 citing papers in PubMed, 143 citations in OpenAlex.
- The cardiac conduction system: development, function and therapeutic targets.Nature reviews. Cardiology · 2026Review
- Article
- New drug discovery of cardiac anti-arrhythmic drugs: insights in animal models.Scientific reports · 2023Article
- Cardiac involvement in patient-specific induced pluripotent stem cells of myotonic dystrophy type 1: unveiling the impact of voltage-gated sodium channels.Frontiers in physiology · 2023Article
- Animal Models to Study Cardiac Arrhythmias.Circulation research · 2022Review
- Association between single-nucleotide polymorphisms ofOpen life sciences · 2022Article
- Review
- Prediction of single-cell mechanisms for disease progression in hypertrophic remodelling by a trans-omics approach.Scientific reports · 2021Article
- Extracellular Matrix Disparities in anFrontiers in cardiovascular medicine · 2020Article
- Nkx2-5 Second Heart Field Target Gene Ccdc117 Regulates DNA Metabolism and Proliferation.Scientific reports · 2019Article
- Furin, a transcriptional target of NKX2-5, has an essential role in heart development and function.PloS one · 2019Article
- Deletion of Nkx2-5 in trabecular myocardium reveals the developmental origins of pathological heterogeneity associated with ventricular non-compaction cardiomyopathy.PLoS genetics · 2018Article
- Transcriptional activator DOT1L putatively regulates human embryonic stem cell differentiation into the cardiac lineage.Stem cell research & therapy · 2018Article
- Point mutations in murineJCI insight · 2017Article
- Development and Function of the Cardiac Conduction System in Health and Disease.Journal of cardiovascular development and disease · 2017Article
- Cardiac disease and arrhythmogenesis: Mechanistic insights from mouse models.International journal of cardiology. Heart & vasculature · 2016Review
- Prolongation of atrio-ventricular node conduction in a rabbit model of ischaemic cardiomyopathy: Role of fibrosis and connexin remodelling.Journal of molecular and cellular cardiology · 2016Article
- The role of transcription factors in atrial fibrillation.Journal of thoracic disease · 2015Review
- NKX2-5, a modifier of skeletal muscle pathology due to RNA toxicity.Human molecular genetics · 2015Article
- Reciprocal myocardial-endocardial interactions pattern the delay in atrioventricular junction conduction.Development (Cambridge, England) · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
A DNA nonbinding mutant of the NK2 class homeoprotein Nkx2.5 dominantly inhibits cardiogenesis in Xenopus embryos, causing a small heart to develop or blocking heart formation entirely. Recently, ten heterozygous CSX/NKX2.5 homeoprotein mutations were identified in patients with congenital atrioventricular (AV) conduction defects. All four missense mutations identified in the human homeodomain led to markedly reduced DNA binding. To examine the effect of a DNA binding-impaired mutant of mouse Csx/Nkx2.5 in the embryonic heart, we generated transgenic mice expressing one such allele, I183P, under the beta-myosin heavy chain promoter. Unexpectedly, transgenic mice were born apparently normal, but the accumulation of Csx/Nkx2.5(I183P) mutant protein in the embryo, neonate, and adult myocardium resulted in progressive and profound cardiac conduction defects and heart failure. P-R prolongation observed at 2 weeks of age rapidly progressed into complete AV block as early as 4 weeks of age. Expression of connexins 40 and 43 was dramatically decreased in the transgenic heart, which may contribute to the conduction defects in the transgenic mice. This transgenic mouse model may be useful in the study of the pathogenesis of cardiac dysfunction associated with CSX/NKX2.5 mutations in humans.
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.