Figure 1. Circadian Gene-mutant Mice Are Cancer-prone.

(a) Representative histological slides of cystic hyperplasia of the uterus, spontaneous ovarian and liver tumors, and lymphoma in the livers of Cry- and Per-mutant mice. (b) All mutant mouse models studied show aging phenotypes on their external appearance after exposure to a 4 Gy sublethal γ-radiation at 6 weeks of age including hair graying, alopecia, ruffled fur, skin lesions, cataracts and eye inflammation, hunchback postures, body weight changes, and sluggish activities. The ages of irradiated mice shown in (b) are: Bmal1^−/− mice at 3–6 months of age, Bmal1^+/− mice at 6–8 months of age, Cry1^−/−;Cry2^−/− mice at 3–6 months of age, Per2 ^−/− mice at 6–8 months of age, Per1^−/−;Per2^m/m mice at 6–8 months of age, and wt littermates at 6–8 months of age. (c) Representative histological slides show lymphoma in the chest cavity of a 20-week old and the salivary gland of a 36-week old irradiated Bmal1^−/− mouse, and the active bone marrow in a 40 week-old irradiated Bmal1^−/− mouse that also displayed aging phenotype on the external appearance. The Kaplan-Meier survival curves of (d) Bmal1^+/− and (e) Per2^−/− mice (−IR: untreated, +IR: irradiated, p1: untreated wt vs. untreated mutant littermates, and p2: irradiated wt vs. irradiated mutant littermates).