ArticlePLoS genetics2009
Tnni3k modifies disease progression in murine models of cardiomyopathy.
Article in PLoS genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
What it found
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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.
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Who cites it
52 citing papers in PubMed, 85 citations in OpenAlex.
- ACE2, CALM3 and TNNI3K polymorphisms as potential disease modifiers in hypertrophic and dilated cardiomyopathies.Molecular and cellular biochemistry · 2018Trial
- High levels of the cardiomyocyte-specific kinase Tnni3k impair zebrafish heart regeneration by driving chronic myocardial inflammation.bioRxiv : the preprint server for biology · 2026Article
- Tnni3k Is Cardioprotective in Viral Myocarditis.Journal of cardiovascular development and disease · 2026Article
- [Dilated cardiomyopathy and conduction disorder due toArchivos de cardiologia de Mexico · 2025Article
- A New Mechanism of Supraventricular Tachycardia: Gene Mutation.Current cardiology reviews · 2025Review
- Unveiling the Spectrum of Minor Genes in Cardiomyopathies: A Narrative Review.International journal of molecular sciences · 2024Review
- A kinase-dead natural polymorphism in the caninemicroPublication biology · 2024Article
- Tnni3k influences cardiomyocyte S-phase activity and proliferation.Journal of molecular and cellular cardiology · 2023Article
- Musings on intrinsic cardiomyocyte cell cycle activity and myocardial regeneration.Journal of molecular and cellular cardiology · 2023Review
- Genome-wide screen identifies host loci that modulate Mycobacterium tuberculosis fitness in immunodivergent mice.G3 (Bethesda, Md.) · 2023Article
- Expression Levels of theInternational journal of molecular sciences · 2023Article
- Genetic Burden ofCirculation. Genomic and precision medicine · 2023Article
- Application of an F0-based genetic assay in adult zebrafish to identify modifier genes of an inherited cardiomyopathy.Disease models & mechanisms · 2023Article
- Cardiomyocyte ploidy is dynamic during postnatal development and varies across genetic backgrounds.Development (Cambridge, England) · 2023Article
- Embryonic Hyperglycemia Disrupts Myocardial Growth, Morphological Development, and Cellular Organization: An In Vivo Experimental Study.Life (Basel, Switzerland) · 2023Article
- Cardiac Troponin I-Interacting Kinase Affects Cardiomyocyte S-Phase Activity but Not Cardiomyocyte Proliferation.Circulation · 2023Article
- Whole-Exome Sequencing Identifies a Novel Variant (c.1538T > C) ofFrontiers in cardiovascular medicine · 2022Article
- The Diverse Roles of TNNI3K in Cardiac Disease and Potential for Treatment.International journal of molecular sciences · 2021Review
- A SPRY1 domain cardiac ryanodine receptor variant associated with short-coupled torsade de pointes.Scientific reports · 2021Article
- The prevalent I686T human variant and loss-of-function mutations in the cardiomyocyte-specific kinase gene TNNI3K cause adverse contractility and concentric remodeling in mice.Human molecular genetics · 2021Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The Calsequestrin (Csq) transgenic mouse model of cardiomyopathy exhibits wide variation in phenotypic progression dependent on genetic background. Seven heart failure modifier (Hrtfm) loci modify disease progression and outcome. Here we report Tnni3k (cardiac Troponin I-interacting kinase) as the gene underlying Hrtfm2. Strains with the more susceptible phenotype exhibit high transcript levels while less susceptible strains show dramatically reduced transcript levels. This decrease is caused by an intronic SNP in low-transcript strains that activates a cryptic splice site leading to a frameshifted transcript, followed by nonsense-mediated decay of message and an absence of detectable protein. A transgenic animal overexpressing human TNNI3K alone exhibits no cardiac phenotype. However, TNNI3K/Csq double transgenics display severely impaired systolic function and reduced survival, indicating that TNNI3K expression modifies disease progression. TNNI3K expression also accelerates disease progression in a pressure-overload model of heart failure. These combined data demonstrate that Tnni3k plays a critical role in the modulation of different forms of heart disease, and this protein may provide a novel target for therapeutic intervention.
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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.