In contrast to previous studies [20,21,22,25,27], our current data revealed that cardiac-specific expression of Cre recombinase caused altered expression of intercalated disc-associated proteins and calcium-signaling-associated proteins, including downregulated N-Cadherin, E-Cadherin and SERCA2 and upregulated β-Catenin and IP3R3, which literally could lead to reduced cardiac contractile function, resulting in irreversible heart failure and the premature death of mice [58,59,60]. The gene discussed is CDH2; the disease is heart failure.