Figure 5. MBNL overexpression partially rescues disrupted ventricular splicing events related to cardiac morphology and function.

(A) Alternative splicing signature scores for ventricle samples. The center line indicates the median value, while the upper and lower dashed lines indicate the first and third quartiles. (B) Number and types of alternative splicing events observed in ventricles. IR, intron retention. (C) Percentage of overlapping CE splicing events in each MBNL-overexpressing cohort using the comparison between CUG960 +/–dox and +dox cohorts as a reference. (D) Genes showing differential alternative splicing changes in comparisons of CUG960 –dox mice with +dox mice, as well as in comparisons of all MBNL cohorts to CUG960 +dox cohort were evaluated for enrichment of GO functional terms using the ShinyGO platform. The dashed vertical line: –log₁₀(FDR) = 1.5 (E) Representative polyacrylamide gels showing alternative splicing changes for the candidate genes Scn5A, Tnnt2, and Ryr2 in ventricles of CUG960 +dox mice that underwent different treatments. (F) Quantification of the PSI for each splicing event. n = 3 animals per cohort. Black lines represent the significant differences in the corresponding groups compared with +dox or tdTomato controls; brown lines represent the significant differences between the corresponding groups and +/–dox and –dox controls. E, exon. Data represent the mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001, by 2-way ANOVA with Tukey’s multiple-comparison test.