2. Academic Validation
  3. Lamin variants cause cardiac arrhythmogenicity in Drosophila

Lamin variants cause cardiac arrhythmogenicity in Drosophila

  • Dis Model Mech. 2025 Jul 1;18(7):dmm052424. doi: 10.1242/dmm.052424.
Stan W van Wijk 1,  Puck Vree 1,  Fabries G Huiskes 1,  Reinier L van der Palen 1,  Aiste Liutkute 2 3 4,  Niels Voigt 2 3 4,  Lori L Wallrath 5,  Bianca J J M Brundel 1
Affiliations

Affiliations

  • 1 Department of Physiology, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Cardiovascular Sciences, Heart Failure and Arrhythmias, 1081 HZ Amsterdam, The Netherlands.
  • 2 Institute of Pharmacology and Toxicology, University Medical Center Göttingen, 37075 Göttingen, Germany.
  • 3 DZHK (German Center for Cardiovascular Research), Partner Site Lower Saxony, 37075 Göttingen, Germany.
  • 4 Cluster of Excellence "Multiscale Bioimaging: From Molecular Machines to Networks of Excitable Cells" (MBExC), University of Göttingen, 37075 Göttingen, Germany.
  • 5 Department of Biochemistry and Molecular Biology, University of Iowa, Iowa City, IA 52242, USA.
PMID: 40605555 DOI: 10.1242/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 investigated how LMNA variants cause cardiac arrhythmicity. Drosophila melanogaster strains were generated possessing the analogous variants in the Drosophila orthologue of human lamin A/C (LMNA), Lamin C (LamC). Heart wall movements in prepupae were recorded before (BTP) and after (ATP) tachypacing. ATP, flies expressing wild-type LamC, and the variants ΔN and p.R205W showed a significant reduction in heart rate (HR), but the arrhythmia index (AI) was not affected, compared to BTP. By contrast, those expressing p.N210K and p.R264Q showed a significant reduction in HR and increased AI, compared to BTP. p.N210K- and p.R264Q-expressing prepupae showed contrasting effects after pharmacological intervention with microtubule stabilizer taxol. Taxol attenuated the arrhythmogenicity in p.N210K-expressing prepupae, but aggravated it in p.R264Q-expressing prepupae. These findings suggest that different lamin variants trigger distinct molecular pathways that drive arrhythmogenic effects in Drosophila.

Keywords

Drosophila melanogaster; Atrial fibrillation; DNA damage; Heart wall; Lamin A/C variants; Microtubules.

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