PRKAG2 and Sinus bradycardia: To gain insights into the pathogenesis of PRKAG2-related sinus bradycardia free of confounders inherent to overexpression transgenesis, we used gene-targeted mice with the R299Q mutation (orthologous to R302Q in humans) introduced into murine Prkag2, permitting the expression and regulation of mutant protein under endogenous control mechanisms (Fig. 1b)9.