This study demonstrates that liver of CrebH−/− mice after DSS treatment show characteristic phenotypes resembling the PSC-liver, as evidenced by increased biliary inflammation, enlarged bile ducts, upregulation of adhesion molecules such as MAdCAM-1, and high similarity of altered genes compared with PSC-liver, suggesting that CrebH−/− mice might be a potential animal model for investigating the initial pathogenesis of liver during the progression of PSC-IBD. Here, MADCAM1 is linked to inflammatory bowel disease.