Related Experiment Video
Updated: Aug 3, 2026
Fluorescent Labeling of Drosophila Heart Structures
Published on: October 13, 2009
Lamin variants cause cardiac arrhythmogenicity in Drosophila
Stan W van Wijk1, Puck Vree1, Fabries G Huiskes1
1Department of Physiology, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Cardiovascular Sciences, Heart Failure and Arrhythmias, 1081 HZ Amsterdam, The Netherlands.
Insights
Genetic variants in LMNA can cause atrial fibrillation (AF). This study used Drosophila models to show distinct cardiac arrhythmicity effects and molecular pathways for different lamin variants.
Area of Science:
- Cardiology
- Genetics
- Molecular Biology
Background:
- Atrial fibrillation (AF) is a common cardiac arrhythmia with serious complications.
- While risk factors are known, 15% of AF cases have a genetic basis.
- The LMNA gene, encoding lamin A/C, is implicated in cardiac function.
Purpose of the Study:
- To investigate how specific LMNA variants contribute to cardiac arrhythmicity.
- To explore the distinct molecular mechanisms underlying variant-induced arrhythmias.
- To utilize Drosophila melanogaster as a model organism for studying laminopathies.
Main Methods:
- Generated Drosophila strains with analogous human LMNA variants in Drosophila Lamin C (LamC).
- Recorded heart wall movements in prepupae before and after tachypacing (BTP and ATP).
- Assessed heart rate (HR) and arrhythmia index (AI), and evaluated effects of taxol intervention.
Main Results:
- Flies expressing wild-type LamC, ΔN, and p.R205W variants showed reduced HR post-tachypacing, with no change in AI.
- Flies expressing p.N210K and p.R264Q variants exhibited reduced HR and increased AI post-tachypacing.
- Taxol treatment differentially affected arrhythmogenicity: it attenuated effects in p.N210K and aggravated them in p.R264Q.
Conclusions:
- Distinct LMNA variants can trigger different molecular pathways leading to cardiac arrhythmicity.
- Drosophila models reveal variant-specific responses to pharmacological interventions.
- These findings advance understanding of genetic contributions to cardiac arrhythmias and potential therapeutic targets.
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.
