We found that after liver-specific knockout of both Smad4 and Pten using the Cre-LoxP mediated approach, Smad4co/co;Ptenco/co;Alb-Cre (abbreviated as SPC) mice started to develop hyperplasia at 2-3 months old, and approximately 22% (2/9) of SPC mice developed CC at 5-6 months old, with some mice also developing HCC after one year of age 7. The gene discussed is SMAD4; the disease is cholangiocarcinoma.