Key result
Cardiac-specific DtnaN49S overexpression in mice increased noncompaction ratio at 4 months (P<0.01) and reduced LVEF at 8 months versus littermate controls (57.57% vs 72.63%, P<0.01).
Why the study?
DTNA encoding dystrobrevin-alpha is a putative causal gene associated with left ventricular noncompaction cardiomyopathy (LVNC), prompting investigation of its causal role in a transgenic mouse model.
Does overexpression of the DTNA-p.N49S mutation cause a phenotype resembling left ventricular noncompaction in a mouse model?
Does overexpression of the DTNA-p.N49S mutation cause a phenotype resembling left ventricular noncompaction in a mouse model?
Overexpression of the DTNA-p.N49S mutation in a mouse model produces a phenotype resembling left ventricular noncompaction, including dilated cardiomyopathy and systolic dysfunction.
Answers are grounded in this paper and cite their sources.
Supports DTNA N49S causality in LVNC mouse model; leaves open human validation before any clinical application.
DTNA encoding dystrobrevin-α (α-DB) is a putative causal gene associated with left ventricular noncompaction cardiomyopathy (LVNC). The aim of the study was to investigate the causal role of DTNA in LVNC using a transgenic mouse model.A missense mutation (c.146A > G, p.N49S) of DTNA was identified in a patient with LVNC by Sanger sequencing. Six independent lines of transgenic mice expressing the mutant DTNA under a myosin heavy chain 6 (Myh6) promoter were generated (Myh6:DtnaN49S). Phenotypic characteristics of DTNA-p.N49S mutations were evaluated by echocardiography, histological observation, and immunoblotting. Multiple trabeculation and a higher ratio of non-compacted to compact myocardial layer were found in the Myh6:DtnaN49S mice compared to the controls. The transgenic mice also showed left ventricular (LV) dilation and cardiac systolic dysfunction. In conclusion, overexpression of the DTNA-p.N49S mutation in a mouse heart can be responsible for the phenotype of deep trabeculation, dilated cardiomyopathy, and cardiac dysfunction, which resembles the phenotype of LVNC.
No takes yet. Share an insight, caveat, or question.
Cao et al. (2017) studied Left ventricular noncompaction cardiomyopathy (LVNC) (n=32). Cardiac-specific overexpression of mutant DTNA (p.N49S / Myh6:DtnaN49S) vs. Littermate control and wild-type (C57Bl/6) mice was evaluated on Left ventricular ejection fraction (LVEF%) in 8-month-old mice (MD -15.06%, p=<0.01). Cardiac-specific DtnaN49S overexpression in mice increased noncompaction ratio at 4 months (P<0.01) and reduced LVEF at 8 months versus littermate controls (57.57% vs 72.63%, P<0.01).
Synapse has enriched 10 related papers. Consider them for comparative context: