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Cx43-S3A is a mutant variant of the gap junction protein Connexin 43 (Cx43), specifically engineered as a phospho-dead version. In this construct, a triplet of serine residues (S273, S279, and S282) is substituted with alanine residues to prevent phosphorylation at these critical regulatory sites. It is primarily utilized in preclinical research, particularly in models of Duchenne muscular dystrophy (DMD), to investigate the role of Cx43 phosphorylation in cardiac pathologies such as fibrosis, arrhythmias, and heart failure. While its counterpart, the phospho-mimic Cx43-S3E, has demonstrated therapeutic potential by preventing pathological remodeling in dystrophic hearts, Cx43-S3A serves as an experimental control that fails to provide such rescue, thereby highlighting the necessity of Cx43 phosphorylation for maintaining cardiac electrical stability and structural integrity.
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