ArticlePLoS genetics2019
Tnni3k alleles influence ventricular mononuclear diploid cardiomyocyte frequency.
Article in PLoS genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 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
27 citing papers in PubMed, 36 citations in OpenAlex.
- Molecular evolution of animal aging.The EMBO journal · 2026Review
- Tnni3k Is Cardioprotective in Viral Myocarditis.Journal of cardiovascular development and disease · 2026Article
- Squamate ventricular cardiomyocytes: Ploidy, proliferation, and heart muscle cell size in the leopard gecko (Eublepharis macularius).Developmental dynamics : an official publication of the American Association of Anatomists · 2025Article
- Revitalizing the heart: strategies and tools for cardiomyocyte regeneration post-myocardial infarction.NPJ Regenerative medicine · 2025Review
- AFrontiers in genetics · 2025Article
- A kinase-dead natural polymorphism in the caninemicroPublication biology · 2024Article
- Transcription factor NFYa controls cardiomyocyte metabolism and proliferation during mouse fetal heart development.Developmental cell · 2023Article
- Review
- Long-Term Transcriptomic Changes and Cardiomyocyte Hyperpolyploidy after Lactose Intolerance in Neonatal Rats.International journal of molecular sciences · 2023Article
- Purkinje Cardiomyocytes of the Adult Ventricular Conduction System Are Highly Diploid but Not Uniquely Regenerative.Journal of cardiovascular development and disease · 2023Article
- Cardiomyocyte ploidy is dynamic during postnatal development and varies across genetic backgrounds.Development (Cambridge, England) · 2023Article
- Cardiac Troponin I-Interacting Kinase Affects Cardiomyocyte S-Phase Activity but Not Cardiomyocyte Proliferation.Circulation · 2023Article
- RBPMS is an RNA-binding protein that mediates cardiomyocyte binucleation and cardiovascular development.Developmental cell · 2022Article
- Polyploidy as a Fundamental Phenomenon in Evolution, Development, Adaptation and Diseases.International journal of molecular sciences · 2022Review
- Gene losses may contribute to subterranean adaptations in naked mole-rat and blind mole-rat.BMC biology · 2022Article
- Article
- IL4Rα signaling promotes neonatal cardiac regeneration and cardiomyocyte cell cycle activity.Journal of molecular and cellular cardiology · 2021Article
- Innate Mechanisms of Heart Regeneration.Cold Spring Harbor perspectives in biology · 2021Review
- Polyploidy in Tissue Repair and Regeneration.Cold Spring Harbor perspectives in biology · 2021Review
- The Diverse Roles of TNNI3K in Cardiac Disease and Potential for Treatment.International journal of molecular sciences · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 6 institutions in 1 country.
Funding
Abstract
Recent evidence implicates mononuclear diploid cardiomyocytes as a proliferative and regenerative subpopulation of the postnatal heart. The number of these cardiomyocytes is a complex trait showing substantial natural variation among inbred mouse strains based on the combined influences of multiple polymorphic genes. One gene confirmed to influence this parameter is the cardiomyocyte-specific kinase Tnni3k. Here, we have studied Tnni3k alleles across a number of species. Using a newly-generated kinase-dead allele in mice, we show that Tnni3k function is dependent on its kinase activity. In an in vitro kinase assay, we show that several common human TNNI3K kinase domain variants substantially compromise kinase activity, suggesting that TNNI3K may influence human heart regenerative capacity and potentially also other aspects of human heart disease. We show that two kinase domain frameshift mutations in mice cause loss-of-function consequences by nonsense-mediated decay. We further show that the Tnni3k gene in two species of mole-rat has independently devolved into a pseudogene, presumably associated with the transition of these species to a low metabolism and hypoxic subterranean life. This may be explained by the observation that Tnni3k function in mice converges with oxidative stress to regulate mononuclear diploid cardiomyocyte frequency. Unlike other studied rodents, naked mole-rats have a surprisingly high (30%) mononuclear cardiomyocyte level but most of their mononuclear cardiomyocytes are polyploid; their mononuclear diploid cardiomyocyte level (7%) is within the known range (2-10%) of inbred mouse strains. Naked mole-rats provide further insight on a recent proposal that cardiomyocyte polyploidy is associated with evolutionary acquisition of endothermy.
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.