Though few significant differences in biliary development were found between Tgm2−/− and WT mice in normal feeding, deficiency of Tgm2 in mice caused the damage of the hallmarks of normal biliary cells such as OPN, acTUB, TGR5, and SSTR2 and even more severe cholestasis in DDC‐induced DR. This evidence concerns the gene SPP1 and cholestasis.