Summary of the Causes of Death for Circadian Gene-mutant Mice.

1Most are B-type lymphomas.
2Hepatocellular adenoma and adenocarcinoma.
3Ovarian granulosa cell tumor.
4Cystic Hyperplasia.
5Renal hydronephrosis and cystic renal dysplasia with severe hydronephrosis.
6Ulcerative necrotizing dermatitis and ulcerative dermatitis with cellulitis and fibrosis, and.
7Aging: untreated Bmal1−/− mice had an average life span of 35 weeks due to severe aging phenotypes, which was reduced to 27 weeks after irradiation.
aSome irradiated/shifted Cry1−/−;Cry2−/−, Per1−/−;Per2m/m and wt mice showed similar aging phenotypes as Bmal1−/− mice and died at 80 weeks of age or older. Some Per- and Cry-mutant and irradiated/jetlagged wt mice developed more than one type of tumors. Other causes of death include lipoma, pancreatic, intestinal and kidney tumors in irradiated/shifted mice, and malnutrition of Bma1l+/−, Cry1−/−;Cry2−/− and Per1−/−;Per2m/m mice due to overgrowth of teeth that prevents food-intake.
p Value: comparison of the number of cases of death caused by osteosarcoma, liver and ovarian tumors, and severe hyperplasia of reproductive organs in each mutant mouse model with wt controls in each category (Students' t-test).
†Wt mice used for all survival curve studies.
•SV: seminal vesicle.
*% mice died due to renal failure.
∧% mice sacrificed due to severe hyperplasia of uterus or enlargement of seminal vesicles (≥20% of total body weight) causing immobility and lack of food intake.
a% mice sacrificed due to severe ulcerative dermatitis on ≥10% of total body surface.
°% mice sacrificed due to aggressive aging resembling Bmal1−/− mice.