All calculations were completed from raw data by two researchers. A standard unpaired t test was used to test all quantitative data, and the Mantel Cox logrank analysis was used for survi val data. Results Kidney tumor severity is age related selleck products and increased in A J Tsc2 mice compared Inhibitors,Modulators,Libraries with C57BL 6 Tsc2 mice In order Inhibitors,Modulators,Libraries to compare kidney disease severity in different Tsc2 mouse strains, we evaluated kidney cystadeno mas in cohorts of A J and C57BL 6 Tsc2 mice at nine and twelve months of age. Kidney disease severity for all cohorts is shown in Figure 1 and Table 1. Untreated A J cohorts are shown in green, and untreated C57BL 6 cohorts are shown in blue. Although data are shown as both average cystadenoma score per kidney and average number of cystadenomas per kidney, these have a similar trend.

The average score per kidney for the A J Tsc2 untreated 12 m cohort is significantly greater than that of the C57BL 6 Tsc2 untreated 12 m cohort. Similarly, the average score per kidney for the A J Tsc2 untreated 9 m cohort is significantly greater than that of the C57BL 6 Tsc2 untreated 9 m cohort. Interestingly, the Inhibitors,Modulators,Libraries average score per kidney for the A J Tsc2 untreated 9 m cohort is significantly greater than that of the C57BL 6 Tsc2 untreated 12 m cohort. Since A J Tsc2 mice have a higher aver age score per kidney at nine months of age than C57BL 6 Tsc2 mice at 12 months of age, these data show that the A J Tsc2 strain has a significantly higher tumor burden than the C57BL 6 Tsc2 strain. There is no significant difference in severity of kidney disease between males and females within the same strain.

This is true for both A J Tsc2 mice and C57BL 6 Tsc2 mice at 9 months of age and 12 months of age. From previous studies, Inhibitors,Modulators,Libraries we have shown that the severity of kidney disease increases with age in C57BL 6 Tsc2 mice. Inhibitors,Modulators,Libraries In order to understand the progression of kidney tumor growth in A J Tsc2 mice, data was col lected at different time best points. The average score per kidney for the A J Tsc2 mice at 3 months, 5 months, and 7 months of age was 6. 5, 33. 0, and 57. 7, respec tively. It is important to note that the score per kidney for the A J Tsc2 untreated 5 m cohort is significantly greater than that of the C57BL 6 Tsc2 untreated 12 m cohort. These data further confirm that the A J Tsc2 strain develops more severe kidney disease than the C57BL 6 Tsc2 strain and will allow for higher through put Tsc2 preclinical studies. Comparison of three rapamycin dosing schedules in Tsc2 mice In a prior preclinical study, we determined that daily rapamycin treatment for two months combined with a rapamycin maintenance dose once a week for five months dramatically reduced tumor burden by 94. 5% as compared to the untreated control.