mTORC1 inhibition rescues the NEX-Tsc2 KO phenotype. A cohort of NEX-Tsc2 mice were treated with RAD001 daily from P1 to P9, killed at P10, and compared with an untreated cohort of the same age. A, RAD001 treatment reduces the body weight of mice with all genotypes, but abolishes the growth deficit observed in the untreated cohort between the KO and WT mice. Bar graphs show the mean values ±SEM; ***p < 0.001. B, Body weight plot of a different cohort of NEX-Tsc2 littermates that were treated with RAD001 daily from P1 to P30, and measured up to P46. Data from WT (n = 1) and HT (n = 3) mice were pooled. KO mice (n = 2) were smaller than controls, but appeared to be healthy. C, Western blot analysis of cortical lysates at P10. RAD001 treatment rescues all signaling defects, including the reduction in Akt phosphorylation and the increase in S6 phosphorylation, as well as the GFAP overexpression seen in untreated KO mice. D, Immunofluorescence analysis of pS6 and GFAP expression in untreated and RAD001-treated KO mice. RAD001 treatment suppresses all staining intensity abnormalities seen in untreated KO mice. Scale bars, 200 µm.