ArticleCardiovascular research2015
Nebulette knockout mice have normal cardiac function, but show Z-line widening and up-regulation of cardiac stress markers.
Article in Cardiovascular research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 32 citations in OpenAlex.
- Unveiling the Spectrum of Minor Genes in Cardiomyopathies: A Narrative Review.International journal of molecular sciences · 2024Review
- Cardiac-targeted delivery of a novel Drp1 inhibitor for acute cardioprotection.Journal of molecular and cellular cardiology plus · 2024Article
- Upregulated α-actinin-1 impairs endometrial epithelial cell adhesion by downregulating NEBL in recurrent implantation failure.iScience · 2024Article
- Nucleus Mechanosensing in Cardiomyocytes.International journal of molecular sciences · 2023Review
- Article
- Structural and signaling proteins in the Z-disk and their role in cardiomyopathies.Frontiers in physiology · 2023Review
- The Mechanisms of Thin Filament Assembly and Length Regulation in Muscles.International journal of molecular sciences · 2022Review
- Understanding the molecular basis of cardiomyopathy.American journal of physiology. Heart and circulatory physiology · 2022Review
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- Article
- Novel insights into sarcomere regulatory systems control of cardiac thin filament activation.The Journal of general physiology · 2021Article
- Deficiency in nebulin repeats of sarcomeric nebulette is detrimental for cardiomyocyte tolerance to exercise and biomechanical stress.American journal of physiology. Heart and circulatory physiology · 2021Article
- LIM-Nebulette Reinforces Podocyte Structural Integrity by Linking Actin and Vimentin Filaments.Journal of the American Society of Nephrology : JASN · 2020Article
- Myopalladin promotes muscle growth through modulation of the serum response factor pathway.Journal of cachexia, sarcopenia and muscle · 2020Article
- Deletion of Enigma Homologue from the Z-disc slows tension development kinetics in mouse myocardium.The Journal of general physiology · 2019Article
- Profiles of differentially expressed genes and overexpression of NEBL indicates a positive prognosis in patients with colorectal cancer.Molecular medicine reports · 2018Article
- Overview of the Muscle Cytoskeleton.Comprehensive Physiology · 2017Review
- Nebulette is a powerful cytolinker organizing desmin and actin in mouse hearts.Molecular biology of the cell · 2016Article
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
aimsNebulette is a 109 kDa modular protein localized in the sarcomeric Z-line of the heart. In vitro studies have suggested a role of nebulette in stabilizing the thin filament, and missense mutations in the nebulette gene were recently shown to be causative for dilated cardiomyopathy and endocardial fibroelastosis in human and mice. However, the role of nebulette in vivo has remained elusive. To provide insights into the function of nebulette in vivo, we generated and studied nebulette-deficient (nebl(-) (/-)) mice. METHODS AND
resultsNebl(-) (/-) mice were generated by replacement of exon 1 by Cre under the control of the endogenous nebulette promoter, allowing for lineage analysis using the ROSA26 Cre reporter strain. This revealed specific expression of nebulette in the heart, consistent with in situ hybridization results. Nebl(-) (/-) mice exhibited normal cardiac function both under basal conditions and in response to transaortic constriction as assessed by echocardiography and haemodynamic analyses. Furthermore, histological, IF, and western blot analysis showed no cardiac abnormalities in nebl(-) (/-) mice up to 8 months of age. In contrast, transmission electron microscopy showed Z-line widening starting from 5 months of age, suggesting that nebulette is important for the integrity of the Z-line. Furthermore, up-regulation of cardiac stress responsive genes suggests the presence of chronic cardiac stress in nebl(-) (/-) mice.
conclusionNebulette is dispensable for normal cardiac function, although Z-line widening and up-regulation of cardiac stress markers were found in nebl(-) (/-) heart. These results suggest that the nebulette disease causing mutations have dominant gain-of-function effects.
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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.