# Transgenic Mouse Model of Congenital Choledochal Cyst

**Authors:** Hannah Nicole Rinehardt, Alexis Martyn, Alexander Kolodychak, Masahiro Takeda, Madison Thomas, Lydia Liszewski, Abigail Rutkowski, Alexander Kreger, George Kingsley Gittes

PMC · DOI: 10.21203/rs.3.rs-7713827/v1 · 2025-10-12

## TL;DR

A new transgenic mouse model was developed to study congenital choledochal cysts and their link to cancer.

## Contribution

A novel transgenic mouse model was created to mimic human choledochal cysts and their oncogenic potential.

## Key findings

- All experimental mice developed a Type I choledochal cyst phenotype.
- MRI confirmed significantly larger bile duct diameters in experimental mice.
- The model mimics the congenital and oncogenic features of human choledochal cysts.

## Abstract

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.

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.

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.

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.

## Linked entities

- **Genes:** TGFA (transforming growth factor alpha) [NCBI Gene 7039]
- **Diseases:** choledochal cyst (MONDO:0018805), cholangiocarcinoma (MONDO:0019087)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Tgfa (transforming growth factor alpha) [NCBI Gene 21802] {aka wa-1, wa1}, Kras (Kras proto-oncogene, GTPase) [NCBI Gene 16653] {aka K-Ras, K-Ras 2, K-ras, Ki-ras, Kras-2, Kras2}
- **Diseases:** Choledochal Cyst (MESH:D015529), Congenital (MESH:D008209), carcinogenesis (MESH:D063646), I (MESH:D006969), bile duct dilation (MESH:D001649), cholangiocarcinoma (MESH:D018281), congenital dilation of the hepatobiliary tree (MESH:D004066), malignancy (MESH:D009369)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]
- **Mutations:** G12D

## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12632577/full.md

---
Source: https://tomesphere.com/paper/PMC12632577