Figure 3.

Genetically modified model animal studies.A, Kaplan–Meier plots of death from cancer from two different studies of mice with clock gene mutations (31, 41). Eight-week-old mice of the indicated genotypes were exposed to 4 Gy of IR at ZT10 and observed for 80 weeks (B) Effect of Cry mutation on cancer incidence and mortality in mouse strains with a predisposition to cancer. Kaplan–Meier plots of death from cancer are shown. Left, p53^−/− (red) and p53^−/−;Cry1/2^–/– (green and blue) survival probabilities. Data shown by the green line have been published (42), and the unpublished data shown by the blue line were obtained by a different member of the lab in a blind experimental design (31). (Right) Tumor-free survival of ink4a^–/–;ras(V12G) (blue) and ink4a^–/–;ras(V12G);Cry1/2^–/– (red) mice. The experiment was conducted in male mice maintained under standard conditions of 12 h light–12 h dark cycles and monitored regularly for the appearance of melanomas. There is no statistically significant difference between the two survival curves (p = 0.2), and hence, it is concluded that in this genetic background Cry mutation has no mitigating effect on cancer incidence or progression. Adapted with permission from Sancar et al. (31).