Work in Progress seminar - PLN-R14del mutation: pathogenetic mechanism in a transgenic mouse model of dilated cardiomyopathy

Claudia Maniezzi, Department of Biotechnology and Biosciences, University of Milano-Bicocca

Zaza’s Lab

The sarco/endoplasmic Ca²⁺ ATPase 2a (SERCA2a) and its inhibitor phospholamban (PLN) play a key role in cardiac excitation-contraction coupling. The heterozygous human PLN-R14del mutation is associated with an arrhythmogenic dilated cardiomyopathy with clinical onset at middle age. We tried to shed light on the pathophysiology by evaluating intracellular Ca²⁺ dynamics and metabolism in ventricular cardiomyocytes isolated from heterozygous (Mut) mice and WT littermates in a presymptomatic stage. Further studies will clarify the interplay between alterations in Ca²⁺ dynamics and mitochondrial derangements in the PLN-R14 del pathogenesis.

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