Transposon-based oncogene integration in Abcb4(Mdr2)^-/- mice recapitulates high susceptibility to cholangiocarcinoma in primary sclerosing cholangitis.

ABSTRACT:

Background & aims

Cholangiocarcinoma (CCA) is a dreaded complication of primary sclerosing cholangitis (PSC) that is difficult to diagnose and associated with high mortality. A lack of animal models of CCA recapitulating the hepatic microenvironment of sclerosing cholangitis has hindered the development of novel treatments. Herein, we sought to develop a mouse model of PSC-associated CCA.

Methods

Ten-week-old Mdr2^-/- mice with congenital PSC-like disease, and healthy wild-type littermates were subjected to either modified retrograde biliary instillation or hydrodynamic tail vein injection of a sleeping beauty transposon-transposase plasmid system with activated AKT (myr-AKT) and Yap (YapS127A) proto-oncogenes (SB AKT/YAP1). The role of TGFβ was interrogated via AL

SUBMITTER: Huang P 

PROVIDER: S-EPMC11655257 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature