Collins, M. M. et al. PNAS 116, 24115–24121 (2019)
GWAS have identified the 4q25 genomic region as a risk locus for atrial fibrillation (AF), and evidence suggests that AF-associated 4q25 variants act by regulating the expression of PITX2, a gene encoding a transcription factor required for cardiac development. Studies using pitx2+/− mice have confirmed the role of PITX2 in AF pathogenesis, but the underlying mechanisms remain unclear.
Here, a team of investigators from the Max Planck Institute and the University of Copenhagen used zebrafish — a model increasingly used to study cardiac diseases, including AF — to further understand the role of PITX2 in AF. By showing that pitx2c−/− zebrafish develop AF phenotypes caused by developmental perturbations to sarcomere organization and metabolic pathways, they provide new insights into the mechanisms of AF.
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Le Bras, A. Studying arrhythmia in zebrafish. Lab Anim 49, 44 (2020). https://doi.org/10.1038/s41684-020-0470-z
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DOI: https://doi.org/10.1038/s41684-020-0470-z