Research square · 2025
Transgenic Mouse Model of Congenital Choledochal Cyst.
СтатьяПрепринтНазвание и аннотация: Перевод в очереди
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Rinehardt Hannah Nicole, Martyn Alexis, Kolodychak Alexander, Takeda Masahiro, Thomas Madison, Liszewski Lydia, Rutkowski Abigail, Kreger Alexander, Gittes George Kingsley
Аннотация
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.
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.