Fig. 5

Characterization of brain-specific SIRT6 knockout and overexpressing mice. a Graphical representation of overrepresented pathways from RNA-sequencing analysis of BSKO, BSOX, and WT brains. All pathways shown were significantly altered after Bonferroni correction (p < 0.05). The number of genes affected from each pathway and the pathway fold enrichment is shown. See also Additional file 2 for complete data analysis. b Pile-up reads of SIRT6 from the RNA-seq analysis. BSKO mice lack reads for exons 2 and 3, while BSOX mice have increased reads at all exons. c Representative SDS-PAGE analysis of brain cortex lysates from BSKO, BSOX, and WT animals is shown. d Bar graph quantification of the ratio of phosphorylated (S473) AKT to total AKT from SDS-PAGE analysis, such as on c, showing a higher ratio (greater AKT activation) in BSKO brains (mean ± SEM, n ≥ 3, *p < 0.05). e Bar graph quantification of full TNFα, such as on C, show lower abundance of full length TNFα in KO brains (mean ± SEM, n ≥ 3, **p < 0.01). f Bar graph quantification of cleaved TNFα, such as on C, show lower abundance of cleaved TNFα in KO brains and greater abundance in OX brains (mean ± SEM, n ≥ 3, **p < 0.01). g, h Relative survival of WT, KO, and OX primary neurons assessed by PI/Annexin-V staining with AKT inhibitor (1 μm) or TNFα receptor inhibitor (100 ng/mL), and or 24 h of MG132 (10 μm) stress. (mean ± SEM, n ≥ 3, *p < 0.05)