Loss of meis2b causes dysmorphic atrial growth and conduction defects.
(a) meis2b-/- larvae exhibit a significant increase in the ratio of atrial to ventricular surface area, while (b) ventricular surface area and (c) body length are not affected compared to WT siblings. (d) Analysis of Tg(myl7:LIFEACT-GFP) fish reveals no obvious defects in atrial myofibrillar architecture in 4 wpf meis2b-/-. (e–h) Adult meis2b-/- display pericardial bulging (arrow) due to abnormal atrial growth. (i) meis2b-/- exhibit a significant increase in atrial cardiomyocyte (CM) proliferation at 3 mpf. (j–k) Cardiac physiology assessed using electrocardiography (ECG) at 5 and 12 mpf. (j) meis2b-/- exhibit a significant increase in PR-segment variability compared to WT siblings, while P-duration and ventricular conduction (QRS) appear unaffected at 5 mpf. (k) At 12 mpf, PR-segment, P-duration and QRS interval are significantly affected in meis2b-/-. (l–m) Representative ECGs of 12 mpf animals show reduced PR-segment duration (red line) and multiple P-waves (arrow) in meis2b-/-. Scale bars: (d) 100 µm, (e–h) 1 mm. (a–c, i) One-tailed student t-tests were performed. (j–k) F-test and Bartlett’s test were performed. Significant differences compared with control are indicated (*p<0.05; **p<0.005; ***p<0.0005); error bars indicate ± SD. A, atrium; V, ventricle; ns, not significant.