Atrial fibrillation (AF)—the most common sustained arrhythmia—is linked to both environmental risk factors and genetic mutations, including those in LMNA, which encodes human Lamin A/C. To explore how LMNA variants contribute to AF pathogenesis, a study in Disease Models & Mechanisms used Drosophila expressing human-equivalent variants of the Lamin C gene (LamC), the fly ortholog of LMNA. Four LamC variants were studied, with the p.N210K and p.R264Q variants showing increased arrhythmicity and reduced heart rate following tachypacing, indicating impaired cardiac function. Treatment with apabetalone (a BRD4 inhibitor) and paclitaxel (a microtubule-stabilizing agent) produced variant-specific effects—suggesting different molecular pathways. These results suggest that lamin variants affect the cardiac cytoskeleton and chromatin organization, contributing to arrhythmia in a variant-dependent manner. This study establishes Drosophila as a functional model for lamin-related AF and to identify therapeutic approaches based on specific LMNA mutations and their molecular consequences.
Original reference: van Wijk, S.W. et al. Dis. Model. & Mech. 18, dmm052424 (2025)
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