Fig. 6

Identification of myh9b as a new deleterious modifier gene for bag3 cardiomyopathy through predicted MMEJ-based genome editing at F0. (A) Ejection fraction (EF) of bag3^e2/e2 fish at 6 months after injection with each of the eight predicted MMEJ-based sgRNAs targeting eight differentially expressed proteostasis/autophagy genes compared to bag3^e2/e2 single-mutant and WT control fish at 6 months; n=4-11, one-way ANOVA. (B,C) Bright-field images of hearts (B) and bar graph (C) showing ventricular surface area (VSA) normalized to body weight (BW) in fish as indicated. The myh9b^MJ-injected bag3^e2/e2 fish (bag3^e2/e2;myh9b^MJ) exhibited increased levels of VSA/BW compared to that in the bag3^e2/e2 mutant alone, myh9b^MJ or non-injected WT controls at 6 months; n=6, one-way ANOVA. Scale bar: 1 mm. (D) Confirmative TEM images to compare hearts of bag3^e2/e2;myh9b^MJ fish to those of bag3^e2/e2 mutant alone, myh9b^MJ or non-injected WT controls at 6 months. Arrows indicate mitochondrial swelling; the asterisk indicates sarcomeric Z-disc aggregation. Scale bar: 2 µM; *P<0.05, ns, not significant.