Authors
van Wijk SW, Vree P, Huiskes FG, van der Palen RL, Liutkute A, Voigt N, Wallrath LL, Brundel BJJM
Journal
Disease Models and Mechanism
Citation
Dis Model Mech. 2025 Jul 3:dmm.052424.
Abstract
Atrial fibrillation (AF), the most common progressive cardiac arrhythmia, is associated with serious complications such as stroke and heart failure. Although common risk factors underlie AF onset, in 15% of the affected population, AF may have a genetic cause. Here we study how LMNA variants cause cardiac arrhythmicity. Hereto, Drosophila melanogaster strains were generated possessing the analogous variants in the Drosophila orthologue of human LMNA, called Lamin C (LamC). Heart wall movements in prepupae were recorded before (BTP) and after tachypacing (ATP). Flies expressing wild type LamC (WT), ΔN, and p.R205W show a significant reduction in heart rate (HR)ATP, but the arrhythmia index (AI)ATP was not affected compared to BTP. By contrast, LamC p.N210K and p.R264Q show a significant reduction in HRATP and increased AIATP compared to BTP. LamC p.N210K and LamC p.R264Q revealed contradicting effects after pharmacological intervention with microtubule stabilizer taxol. Taxol attenuates the arrhythmogenic effect of LamC p.N210K, but aggravates it in p.R264Q. The findings suggest that different lamins variants trigger distinct molecular pathways that drive arrhythmogenic effects in Drosophila.
DOI
10.1242/dmm.052424
Pubmed Link
