Fig. 4: Reduction of Rptor prolongs the lifespan of Tsc1-cKO mice.

a Representative image showing one hemisphere of a coronal section from an Emx1-Cre⁺;Ai9⁺ mouse. The Cre-dependent tdTomato reporter is in red. DAPI labels cell nuclei (blue). This experiment was performed once. Scale bar = 1 mm. b Schematic of the crosses used to generate experimental mice. Emx1-Cre^wt/+ mice were crossed with Tsc1^wtl/fl mice. This line was then bred to either Rictor^wt/fl or Rptor^wt/fl mice. Created with BioRender.com. c, d Survival analysis of Tsc1;Rptor;Emx1-Cre (c) and Tsc1;Rictor;Emx1-Cre (d) mice of the indicated genotypes. The starting number of mice for each genotype is indicated in parentheses. Dashed lines indicate 50% of the population surviving. P values from Log-rank Mantel–Cox tests are shown. e–h Mean ± SEM body weight in grams measured from postnatal day 11–40 for mice of the indicated sex and genotype. The starting number of mice for each genotype and sex is indicated in parentheses. f = females, m = males. Mixed-effect model (REML) with Geisser-Greenhouse correction statistics: Tsc1;Rptor;Emx1-Cre females (e), day p < 0.0001, F(1.447, 51.30) = 398.9; geno p = 0.0036, F(3, 45) = 5.192. Tsc1;Rptor;Emx1-Cre males (f), day p < 0.0001, F(2.287, 79.03) = 197.4; geno p < 0.0001, F(3, 45) = 26.85. Tsc1;Rictor;Emx1-Cre females (g), day p < 0.0001, F(4.257, 69.52) = 221.1; geno p < 0.0001, F(3, 30) = 53.74. Tsc1;Rictor;Emx1-Cre males (h), day p < 0.0001, F(2.389, 48.04) = 370.4; geno p < 0.0001, F(3, 41) = 28.86. Multiple comparisons testing was not performed. See also Supplementary Figs. 5, 9 and Supplementary Tables 1, 2. Source data are provided as a Source Data file.