There are also some genetically engineered mouse models of iCCA, such as liver-specific targeted disruption of tumor suppressors Smad4 and Pten (Alb-Cre/Smad4loxP/floxP/PtenloxP/floxP) (62), tissue-specific activation of Kras and deletion of p53 (Alb-Cre/loxP-stop-loxP-KrasG12D/p53loxP/loxP) (63), and liver-specific Kras activation and Pten deletion (Alb-Cre/PtenloxP/loxP/loxP-stop-loxP-KrasG12D) (64, 65). This evidence concerns the gene PTEN and neoplasm.