Using bigenic the AFP-Notch Intracellular Domain (AFP-NICD) mice, in which Cre-mediated recombination in embryonic hepatoblasts results in the expression of a constitutively active form of Notch1 in >95% of cholangiocytes and hepatoblasts, Villanueva et al. showed HCC development in 100% of mice [29]. The gene discussed is AFP; the disease is hepatocellular carcinoma.