ArticleeLife2015
An internal promoter underlies the difference in disease severity between N- and C-terminal truncation mutations of Titin in zebrafish.
Article in eLife, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 107 citations in OpenAlex.
- Mending the Achilles heels of titin in cardiac and musculoskeletal disease.Biophysical reviews · 2026Review
- Location-Dependent Differences in Cardiac and Skeletal Muscle Dysfunction Associated With Truncating Titin (Circulation research · 2026Article
- Molecular identifiers of the evolutionarily conserved titin pseudokinase.The Biochemical journal · 2026Article
- Zebrafish as a Model Organism for Research in Rare Genetic Neuromuscular Diseases.International journal of molecular sciences · 2025Review
- Cartilaginous fish and mammalian connectin evolved independently from an ancestral bony fish-like structure.Scientific reports · 2025Article
- In Vivo Approaches to Understand Arrhythmogenic Cardiomyopathy: Perspectives on Animal Models.Cells · 2024Review
- Loss of connectin novex-3 leads to heart dysfunction associated with impaired cardiomyocyte proliferation and abnormal nuclear mechanics.Scientific reports · 2024Article
- Article
- Allelic heterogeneity of TTNtv dilated cardiomyopathy can be modeled in adult zebrafish.JCI insight · 2024Article
- Titin: roles in cardiac function and diseases.Frontiers in physiology · 2024Review
- Deletion of taf1 and taf5 in zebrafish capitulate cardiac and craniofacial abnormalities associated with TAFopathies through perturbations in metabolism.Biology open · 2023Article
- Transcriptome studies of inherited dilated cardiomyopathies.Mammalian genome : official journal of the International Mammalian Genome Society · 2023Review
- Advances in symptomatic therapy for left ventricular non-compaction in children.Frontiers in pediatrics · 2023Review
- Optical transparency and label-free vessel imaging of zebrafish larvae in shortwave infrared range as a tool for prolonged studying of cardiovascular system development.Scientific reports · 2022Article
- Titin (TTN): from molecule to modifications, mechanics, and medical significance.Cardiovascular research · 2022Review
- Use of animal models to understand titin physiology and pathology.Journal of cellular and molecular medicine · 2022Review
- Titin-related Cardiomyopathy: Is it a Distinct Disease?Current cardiology reports · 2022Review
- Article
- Reading Frame Repair ofCirculation · 2022Article
- Modeling Human Cardiac Arrhythmias: Insights from Zebrafish.Journal of cardiovascular development and disease · 2022Review
Corrections and comments
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Authors and funding
25 authors at 5 institutions in 2 countries.
Funding
Abstract
Truncating mutations in the giant sarcomeric protein Titin result in dilated cardiomyopathy and skeletal myopathy. The most severely affected dilated cardiomyopathy patients harbor Titin truncations in the C-terminal two-thirds of the protein, suggesting that mutation position might influence disease mechanism. Using CRISPR/Cas9 technology, we generated six zebrafish lines with Titin truncations in the N-terminal and C-terminal regions. Although all exons were constitutive, C-terminal mutations caused severe myopathy whereas N-terminal mutations demonstrated mild phenotypes. Surprisingly, neither mutation type acted as a dominant negative. Instead, we found a conserved internal promoter at the precise position where divergence in disease severity occurs, with the resulting protein product partially rescuing N-terminal truncations. In addition to its clinical implications, our work may shed light on a long-standing mystery regarding the architecture of the sarcomere.
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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.