Extended Data Fig. 1: Selective inhibition of mTORC1 or mTORC2 activity in Pten fb-KO mice.
(a) Schematics of generation of forebrain neuron specific Pten-deficient (Pten fb-KO) and double knockout mice (Pten-Rptor fb-DKO and Pten-Rictor fb-DKO). (b-e) Representative western blot (b) and quantification show reduced PTEN levels in Pten fb-KO mice (c, n = 5, t = 5.22, P < 0.0001), Pten-Rptor fb-DKO (c, n = 5, t = 5.34, P < 0.0001) and Pten-Rictor fb-DKO (c, n = 5, t = 4.50, P = 0.0004) and reduced Raptor (d, n = 5 per group, vs. control t = 3.52, P = 0.0028) or Rictor (e, n = 5, t = 3.83, P = 0.0015) levels in the hippocampus of Pten-Rptor fb-DKO mice or Pten-Rictor fb-DKO mice, respectively. Representative western blot (f) and quantification (g-h) show increased mTORC1 (g, p-S6 at S240/244) and mTORC2 activity (h, p-Akt at S473) in cortex of Pten fb-KO mice (n = 6 per group, p-S6: t = 2.32, P = 0.03, p-Akt: t = 2.81, P = 0.0111). The increased mTORC1 activity in the cortex of Pten fb-KO mice was reduced in Pten-Rptor fb-DKO mice (n = 6, vs. Pten fb-KO, t = 2.87, P = 0.0091), but not in Pten-Rictor fb-DKO mice (n = 6, vs. Pten fb-KO, t = 0.13, P = 0.8958). By contrast, the increased mTORC2 activity in the cortex of Pten fb-KO mice was reduced in Pten-Rictor fb-DKO mice (t = 3.02, P = 0.0066), but not in Pten-Rptor fb-DKO mice (t = 3.92, P = 0.0009). Data are mean ± SEM. Statistics were based on one-way ANOVA followed by uncorrected two-sided Fisher’s LSD method for pairwise comparisons. n.s., not significant.
