ArticleThe Journal of clinical investigation1999
Cardiac troponin T mutations result in allele-specific phenotypes in a mouse model for hypertrophic cardiomyopathy.
Article in The Journal of clinical investigation, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers.
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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
114 citing papers in PubMed, 235 citations in OpenAlex.
- Galangin 3-methyl ether alleviates mouse hypertrophic cardiomyopathy via targeting HDAC2 and subsequently inactivating the PI3K-AKT signaling pathway.Acta pharmacologica Sinica · 2026Article
- Article
- Protein interactions, network pharmacology, and machine learning work together to predict genes linked to mitochondrial dysfunction in hypertrophic cardiomyopathy.Scientific reports · 2025Article
- Experimental Models of Hypertrophic Cardiomyopathy: A Systematic Review.JACC. Basic to translational science · 2025Review
- Reduction in myofilament CaFrontiers in physiology · 2025Article
- Arg92Leu-cTnT Alters the cTnC-cTnI Interface Disrupting PKA-Mediated Relaxation.Circulation research · 2024Article
- Substrate mechanics unveil early structural and functional pathology in iPSC micro-tissue models of hypertrophic cardiomyopathy.iScience · 2024Article
- Modeling cardiomyocyte signaling and metabolism predicts genotype-to-phenotype mechanisms in hypertrophic cardiomyopathy.Computers in biology and medicine · 2024Article
- Allele-specific dysregulation of lipid and energy metabolism in early-stage hypertrophic cardiomyopathy.Journal of molecular and cellular cardiology plus · 2024Article
- Single-nucleus RNA/ATAC-seq in early-stage HCM models predicts SWI/SNF-activation in mutant-myocytes, and allele-specific differences in fibroblasts.bioRxiv : the preprint server for biology · 2024Article
- AnBioMed research international · 2024Article
- Molecular Pathways and Animal Models of Cardiomyopathies.Advances in experimental medicine and biology · 2024Article
- Mechano-energetic uncoupling in hypertrophic cardiomyopathy: Pathophysiological mechanisms and therapeutic opportunities.Journal of molecular and cellular cardiology plus · 2023Review
- Mechanisms of Sarcomere Protein Mutation-Induced Cardiomyopathies.Current cardiology reports · 2023Review
- Genome Editing and Pathological Cardiac Hypertrophy.Advances in experimental medicine and biology · 2023Article
- Cardiac Sarcomere Signaling in Health and Disease.International journal of molecular sciences · 2022Review
- Low expression of the K280NJournal of molecular and cellular cardiology plus · 2022Article
- Partial and complete loss of myosin binding protein H-like cause cardiac conduction defects.Journal of molecular and cellular cardiology · 2022Article
- Effects of Sarcomere Activators and Inhibitors Targeting Myosin Cross-Bridges on CaMolecular pharmacology · 2022Article
- Small Molecule RPI-194 Stabilizes Activated Troponin to Increase the Calcium Sensitivity of Striated Muscle Contraction.Frontiers in physiology · 2022Article
54 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Multiple mutations in cardiac troponin T (cTnT) can cause familial hypertrophic cardiomyopathy (FHC). Patients with cTnT mutations generally exhibit mild or no ventricular hypertrophy, yet demonstrate a high frequency of early sudden death. To understand the functional basis of these phenotypes, we created transgenic mouse lines expressing 30%, 67%, and 92% of their total cTnT as a missense (R92Q) allele analogous to one found in FHC. Similar to a mouse FHC model expressing a truncated cTnT protein, the left ventricles of all R92Q lines are smaller than those of wild-type. In striking contrast to truncation mice, however, the R92Q hearts demonstrate significant induction of atrial natriuretic factor and beta-myosin heavy chain transcripts, interstitial fibrosis, and mitochondrial pathology. Isolated cardiac myocytes from R92Q mice have increased basal sarcomeric activation, impaired relaxation, and shorter sarcomere lengths. Isolated working heart data are consistent, showing hypercontractility and diastolic dysfunction, both of which are common findings in patients with FHC. These mice represent the first disease model to exhibit hypercontractility, as well as a unique model system for exploring the cellular pathogenesis of FHC. The distinct phenotypes of mice with different TnT alleles suggest that the clinical heterogeneity of FHC is at least partially due to allele-specific mechanisms.
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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.