Mouse models of primary sclerosing cholangitis: we just can't get enough

Primary sclerosing cholangitis (PSC) is a rare but devastating disease affecting the intra- and extrahepatic bile ducts, frequently progressing to end-stage liver disease. Patients develop peribiliary inflammation and fibrosis, leading to multifocal biliary strictures that evolve to biliary cirrhosis. PSC is frequently associated with inflammatory bowel disease and a high risk of cholangiocarcinoma development. The pathogenesis of this disease is not completely understood, and currently, there are no effective therapies beyond liver transplantation. The available experimental models of PSC do not fully reproduce the phenotype of the disease, and this is a major limitation for unraveling its pathogenic mechanisms and evaluating novel therapies. A recent study by Lukasova etal. proposed a new hypothesis on the pathogenesis of PSC. The relevance of their work is two-fold: (1) the authors provide preliminary evidence suggesting that the disruption of tight junctions in mouse biliary epithelium leads to a PSC-like phenotype; and (2) they provide the research community with a novel transgenic mouse model of the disease. Follow-up studies on this new mouse model are eagerly awaited.