Transgenic mouse model of congenital choledochal cyst.

PURPOSE: Choledochal cyst is a rare, congenital dilation of the hepatobiliary tree. Due to the associated malignancy risk, complete resection is recommended. There remains a risk of metachronous cholangiocarcinoma despite resection necessitating lifelong surveillance. Choledochal cysts are increasingly prevalent with an incompletely understood connection to carcinogenesis. We sought to develop a mouse model to reliably mimic human disease process of choledochal cyst. METHODS: Experimental transgenic mice were bred with a genotype of Pdx-Cre, TGFα, LSL-Kras G12D Mu/Wt. Control C57 mice were used as a comparison. Experimental and control mice underwent serial abdominal magnetic resonance imaging (MRI) from weaning to sacrifice. RESULTS: All experimental mice developed fusiform extrahepatic common bile duct dilation most consistent with Todani Type Ic (fusiform) choledochal malformation. Choledochal cyst was present on imaging modalities upon weaning. Maximum common bile duct (CBD) diameter by MRI demonstrated a significantly larger diameter in the experimental group compared to the control group at 10 weeks. CONCLUSION: All experimental mice with a genotype of Pdx-Cre, TGFα, LSL-Kras Mu/Wt developed a phenotype consistent with congenital choledochal cyst. This transgenic mouse model mimics the oncogenic nature of choledochal cyst and could be used to further study disease pathophysiology and novel interventions.