Transgenic Mouse Model of Congenital Choledochal Cyst

Abstract 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 mimicking a Type I choledochal cyst. 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.