SMAD4 and cholangiocarcinoma: Other reported genetically engineered mouse CCA models included mice with constitutive expressions of the human epidermal growth factor receptor 2 (ERBB2), mice with hepatocyte-specific disruption of tumor suppressors SMAD4 and PTEN, carbon tetrachloride-administered p53 knockout mice, and mice with hepatocyte-specific constitutive Notch1 expression [27,28,29,30].