APC and colorectal carcinoma: To explore the therapeutic role of USP7 in CRC, we first examined the effect of Usp7 deletion in an acute WNT activation model mediated by homozygous loss of Apc. VillinCreERT2;Apcfl/fl (Apcfl/fl) mice (Shibata et al., 1997) were crossed with VillinCreERT2;Usp7fl/fl mice (Kon et al., 2011) to obtain intestinal-specific conditional deletion of Apc and Usp7. Homozygous loss of Apc caused hyperproliferation of the intestinal crypts within 6 days after tamoxifen induction (Figures 1A, 1B, 1D, and 1E).