ArticleThe Journal of clinical investigation2015
Normalization of Naxos plakoglobin levels restores cardiac function in mice.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 43 citations in OpenAlex.
- Lipid Metabolism as a Therapeutic Target in Arrhythmogenic Cardiomyopathy: Emerging Therapeutic Implications of Lipid-Lowering Therapy.Reviews in cardiovascular medicine · 2026Review
- PNPLA2 gene therapy resolves myocardial lipid deposition in arrhythmogenic cardiomyopathy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- In Vivo Approaches to Understand Arrhythmogenic Cardiomyopathy: Perspectives on Animal Models.Cells · 2024Review
- Plakophilin 2 gene therapy prevents and rescues arrhythmogenic right ventricular cardiomyopathy in a mouse model harboring patient genetics.Nature cardiovascular research · 2023Article
- Lem2 is essential for cardiac development by maintaining nuclear integrity.Cardiovascular research · 2023Article
- Dynamic mechanobiology of cardiac cells and tissues: Current status and future perspective.Biophysics reviews · 2023Review
- Towards a Better Understanding of Genotype-Phenotype Correlations and Therapeutic Targets for Cardiocutaneous Genes: The Importance of Functional Studies above Prediction.International journal of molecular sciences · 2022Review
- Animal Models to Study Cardiac Arrhythmias.Circulation research · 2022Review
- Understanding the molecular basis of cardiomyopathy.American journal of physiology. Heart and circulatory physiology · 2022Review
- Cardiomyocyte Expression of ZO-1 Is Essential for Normal Atrioventricular Conduction but Does Not Alter Ventricular Function.Circulation research · 2020Article
- Atypical ALPK2 kinase is not essential for cardiac development and function.American journal of physiology. Heart and circulatory physiology · 2020Article
- A signaling hub of insulin receptor, dystrophin glycoprotein complex and plakoglobin regulates muscle size.Nature communications · 2020Article
- Genetic Animal Models for Arrhythmogenic Cardiomyopathy.Frontiers in physiology · 2020Review
- Mechanotransduction and Adrenergic Stimulation in Arrhythmogenic Cardiomyopathy: An Overview ofFrontiers in physiology · 2020Review
- Molecular mechanisms of arrhythmogenic cardiomyopathy.Nature reviews. Cardiology · 2019Review
- P209L mutation in Bag3 does not cause cardiomyopathy in mice.American journal of physiology. Heart and circulatory physiology · 2019Article
- Linker of nucleoskeleton and cytoskeleton complex proteins in cardiomyopathy.Biophysical reviews · 2018Review
- Luma is not essential for murine cardiac development and function.Cardiovascular research · 2018Article
- Generation and Analysis of Striated Muscle Selective LINC Complex Protein Mutant Mice.Methods in molecular biology (Clifton, N.J.) · 2018Article
- Loss-of-function mutations in co-chaperone BAG3 destabilize small HSPs and cause cardiomyopathy.The Journal of clinical investigation · 2017Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
Arrhythmogenic cardiomyopathy (AC) is associated with mutations in genes encoding intercalated disc proteins and ultimately results in sudden cardiac death. A subset of patients with AC have the autosomal recessive cardiocutaneous disorder Naxos disease, which is caused by a 2-base pair deletion in the plakoglobin-encoding gene JUP that results in a truncated protein with reduced expression. In mice, cardiomyocyte-specific plakoglobin deficiency recapitulates many aspects of human AC, and overexpression of the truncated Naxos-associated plakoglobin also results in an AC-like phenotype; therefore, it is unclear whether Naxos disease results from loss or gain of function consequent to the plakoglobin mutation. Here, we generated 2 knockin mouse models in which endogenous Jup was engineered to express the Naxos-associated form of plakoglobin. In one model, Naxos plakoglobin bypassed the nonsense-mediated mRNA decay pathway, resulting in normal levels of the truncated plakoglobin. Moreover, restoration of Naxos plakoglobin to WT levels resulted in normal heart function. Together, these data indicate that a gain of function in the truncated form of the protein does not underlie the clinical phenotype of patients with Naxos disease and instead suggest that insufficiency of the truncated Naxos plakoglobin accounts for disease manifestation. Moreover, these results suggest that increasing levels of truncated or WT plakoglobin has potential as a therapeutic approach to Naxos disease.
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