A) Knockout (KO) of Trdn-as by CRISPR/Cas9 genome editing. Trdn exons are shown in green and Trdn-as in red. B) Deletion of Trdn-as in hearts of two KO lines, line 1 and line 2 confirmed by qPCR. Each filled circle represents one mouse. Data are presented as mean ± SD. C-D) Left ventricular ejection fraction (EF) by echocardiography and running distance of indicated mice. Mice ran at speeds of 15, 25, 28, 31, 34, 37, and 40 m/min, each for 1 minute until mice were exhausted. Each filled circle represents one mouse. Data are presented as mean ± SD. One-way ANOVA with Tukey’s post test; *p = 0.05, **p < 0.05, ***p < 0.01, ns: not significant. E) Kaplan-Meier survival curve for WT (n = 11) and Trdn-as KO (n = 12) mice by OASIS2. Log-Rank test; *p<0.05. Both males and females were used for these assays.