Fig. 3

ASO-mediated Upf3b depletion is well tolerated in normal mice. Mice (n = 4) were treated with an Upf3b-ASO at 50, 100, or 150 mg/kg/week. DPBS and a scrambled ASO dosed at 150 mg/kg/week were used as controls. Animals were dosed twice a week for total of eight doses in a 4-week period. Necropsy was performed 48 h after the last dose of ASO. Results are presented as means ± standard errors. a Body weights of the mice over the course of the study. b Plasma ALT and AST levels as measured by clinical analyzer at necropsy. c Liver, kidney, and spleen weights measured at necropsy. d qPCR analysis of Upf3b mRNA levels in mouse liver samples. Mouse Gapdh mRNA was used as endogenous control. Upf3b mRNA level in DPBS treated animals was set as 1. e Western blot analysis of UPF3B protein levels in mouse liver samples with UPF3B-specific antibody. Top: Odyssey (LI-COR) images of the western blot. Bottom: Image studio quantification of the western blot image in the upper panel. β-ACTIN protein levels were used as loading controls. UPF3B protein level in DPBS treated animals was set as 100%. Statistical significance was determined using a two-way ANOVA and Dunnett’s multiple comparison test in Prism. All groups were compared to DPBS-treated mice. **** p < 0.0001. mpk mg/kg