Fig. 3: Pkp2-cKO ARVC mouse model recapitulated the majority of human ARVC clinical manifestations.
a Pkp2-cKO ARVC mice (αMyHC-Cre-ER(T2), Pkp2fl/fl)31 at ~3 months of age were injected with tamoxifen to induce cardiac knock-out of the Pkp2 gene. Representative immunoblots showed reduction of desmosome proteins PKP2, DSP, JUP, and GJ protein, Cx43. b Pkp2-cKO mice developed spontaneous PVCs as observed during 30 min of continuous recording of EKG and reported in the table. Statistical evaluation using nonparametric Kruskal-Wallis test with Dunn’s correction showed a significant increase in PVC counts from week 1 to week 3 (p = 0.0004). c LV performance measured by % ejection fraction sharply declined at 2 weeks post tamoxifen induction. d Pkp2-cKO mice started to develop biventricular dilatation between 2 and 3 weeks post tamoxifen induction. RV area (left panel) and LV internal diameter end diastole (LVIDd, right panel) were normalized to body weight. e Kaplan-Meier survival curve showed a sharp decline of survival of Pkp2-cKO mice beginning 3 weeks post tamoxifen induction. Animals showed symptoms including sudden death, edema, reduced activity, and reduced tolerance to isoflurane beginning 3 weeks post induction. Quantified data were presented as mean ± s.e.m. P value: Ordinary Two-Way ANOVA (Tukey’s post-hoc test); **p = 0.002, ****p < 0.0001 vs. WT at 2, 3, and 4 weeks, respectively. Sample size n = 4 and 7 for WT and Pkp2-cKO, respectively.
