Fig. 8
SGK1 inhibition rescues a zebrafish model of long QT. (A) Still frame image of zebrafish heart with chamber labels (A = atrium) (V = ventricle). Representative tracings of chamber wall position demonstrating 2:1 AV block in mutant bkd −/− zebrafish (upper panel) and with rescue of the phenotype (lower panel). (B) Knock-down with SGK1 morpholino or inhibition of SGK1 (500 μM SGK1-DN mRNA) in the breakdance zebrafish mutants with long QT at 1–2 cell stage leads to significant rescue of 2:1 AV block at 99 hpf stage (5% spontaneous reversion at this stage); *p-value < 0.05 by Z-test. (C) Compound 5377051 added at 48 hours post fertilization (hpf) and assessed at 72 hpf for rescue of phenotype 2 with superimposed rescue (solid line) and toxicity (dashed lines) curves shown on left (C) and representative bar graph on right (D). *p < 0.05 by Z-test.