Fig. 4: Knockout of the Scn10a (NaV1.8) gene in CaMKIIδc+/T mice improves survival.
a Survival curve of CaMKIIδc+/T and SCN10A−/−/CaMKIIδc+/T (43 vs. 64 animals, median survival 72 vs. 98 days, blinded analysis). Log-rank (Mantel–Cox test and Gehan–Breslow–Wilcoxon test (two-tailed analysis) were performed to calculate the survival percentage of mice. Probability vs CaMKIIδc+/T. b Hearts from WT, SCN10A−/−, CaMKIIδc+/T, and SCN10A−/−/CaMKIIδc+/T mice. c Ratio of heart weight to tibia length as a parameter of cardiac hypertrophy. CaMKIIδc+/T and SCN10A−/−/CaMKIIδc+/T showed a significant increase in this ratio compared to WT and SCN10A−/− mice. Data were analyzed by one-way ANOVA with post hoc Bonferroni’s correction. (N = hearts studied, WT = 14, SCN10A−/− = 16, CaMKIIδc+/T = 13, and SCN10A−/−/CaMKIIδc+/T = 23). Data were presented as mean values ± SEM. d Original histological wheat germ agglutinin staining from WT, SCN10A−/−, CaMKIIδc+/T, and SCN10A−/−/CaMKIIδc+/T mice. Scale bars = 75 µm. Stainings were produced from different sections and three different regions (basal, mid-ventricular, and apical) of each heart studied. e Cardiomyocyte cross-sectional-area (CSA) as a parameter for cellular hypertrophy. CaMKIIδc+/T and SCN10A−/−/CaMKIIδc+/T showed a significant increase in CSA compared to WT and SCN10A−/− mice. CSA in CaMKIIδc+/T and SCN10A−/−/CaMKIIδc+/T mice did not significantly differ. Data were analyzed by one-way ANOVA with post hoc Bonferroni’s correction. N = hearts studied (>300 cardiomyocytes were studied per heart, from different sections and different regions (basal, mid-ventricular, apical), WT = 5 hearts, SCN10A−/− = 5 hearts, CaMKIIδc+/T = 4 hearts, SCN10A−/−/CaMKIIδc+/T = 5 hearts. Data were presented as mean values ± SEM. f Original echocardiography recordings from WT, SCN10A−/−, CaMKIIδc+/T, and SCN10A−/−/CaMKIIδc+/T at M-mode in 12–13- week-old mice. g Echocardiography recordings revealed a decrease in left ventricular ejection fraction (EF) in CaMKIIδc+/T (six mice) and SCN10A−/−/CaMKIIδc+/T (six mice) compared to WT (seven mice) or SCN10A−/− (eight mice) (p < 0.0001(one-way ANOVA with post hoc Bonferroni’s correction). Data were presented as mean values ± SEM. h Echocardiography recordings revealed a significant increase in left ventricular end-diastolic diameter (LVEDD) in CaMKIIδc+/T (six mice) and SCN10A−/−/CaMKIIδc+/T (six mice) compared to WT (seven mice) or SCN10A−/− (eight mice) (p < 0.0001). LVEDD was not significantly different in WT vs SCN10A−/− or CaMKIIδc+/T vs SCN10A−/−/CaMKIIδc+/T (one-way ANOVA with post hoc Bonferroni’s correction). Data were presented as mean values ± SEM.
