- Title
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A mutation in the atrial-specific myosin light chain gene (MYL4) causes familial atrial fibrillation
- Authors
- Orr, N., Arnaout, R., Gula, L.J., Spears, D.A., Leong-Sit, P., Li, Q., Tarhuni, W., Reischauer, S., Chauhan, V.S., Borkovich, M., Uppal, S., Adler, A., Coughlin, S.R., Stainier, D.Y., Gollob, M.H.
- Source
- Full text @ Nat. Commun.
Electrocardiograms and whole hearts from WT transgenic and E17K transgenic zebrafish. (a) WT transgenics exhibit a regular heart rate with electrocardiogram parameters typical for adult zebrafish. E17K transgenics display significantly slower sino-atrial activity and increased heart rate irregularity compared with controls. (b) Signal-averaged P-wave duration is prolonged in E17K transgenics, indicative of slower atrial conduction time. (c) Atrial area has been traced in isolated whole-WT transgenic and -E17K transgenic hearts (dotted lines), showing enlarged atrial chamber size in E17K transgenic. PHENOTYPE:
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Myofibrillar organization and sarcomeric structure in WT and E17K transgenics. (a) A WT transgenic atrium at larval stage (5 d.p.f.) in the Tg(myl7:LifeAct-GFP)s974 background shows GFP-labelled F-actin, with myofibrils organized linearly across the atrium, either up-and-down or left-to-right. The myofibrils have a ‘dotted line’ pattern, with well-demarcated box-like shapes indicating normal arrangement of F-actin in the myofibrils. The non-fluorescent gaps (arrows) represent the actin-poor H-zones. (b) In an E17K transgenic larval atrium, some myofibrils appear unaffected (arrows), but there are large areas where myofibrils are not linearly organized and actin localization appears abnormal, giving a stippled appearance to the sarcomeres without clear H-zones (arrowheads). (c) Electron microscopy of adult WT zebrafish atrium shows clear H-zones and Z-disks. (d) Electron microscopy of E17K transgenic atrium shows preserved H-zones but absent Z-disks (arrows). H, H-zone. Z, Z-disk. |
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