Journal article
Lamin variants cause cardiac arrhythmogenicity in Drosophila
Disease models & mechanisms, Vol.18(7), dmm052424
07/01/2025
DOI: 10.1242/dmm.052424
PMCID: PMC12320974
PMID: 40605555
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.
Details
- Title: Subtitle
- Lamin variants cause cardiac arrhythmogenicity in Drosophila
- Creators
- Stan W van Wijk - Amsterdam University Medical CentersPuck Vree - Amsterdam University Medical CentersFabries G Huiskes - Vrije Universiteit AmsterdamReinier L van der Palen - Amsterdam University Medical CentersAiste Liutkute - University of GöttingenNiels Voigt - Universitätsmedizin GöttingenLori L Wallrath - University of IowaBianca J J M Brundel - Amsterdam University Medical Centers
- Resource Type
- Journal article
- Publication Details
- Disease models & mechanisms, Vol.18(7), dmm052424
- DOI
- 10.1242/dmm.052424
- PMID
- 40605555
- PMCID
- PMC12320974
- NLM abbreviation
- Dis Model Mech
- ISSN
- 1754-8411
- eISSN
- 1754-8411
- Publisher
- The Company of Biologists
- Grant note
- Muscular Dystrophy Association Deutsches Zentrum fur Herz-Kreislaufforschung Nederlandse Organisatie voor Wetenschappelijk Onderzoek Hartstichting
- Language
- English
- Electronic publication date
- 07/03/2025
- Date published
- 07/01/2025
- Academic Unit
- Biochemistry and Molecular Biology; University College Courses
- Record Identifier
- 9984843595502771
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