Fig. 4

Blocking TDP-43 SUMOylation at K408 in vivo leads to sex-specific social and cognitive impairment in female mice. A Representative image of a barbered female mouse and quantification of cumulative barbering probability. 2-Way ANOVA with Tukey’s Multiple Comparisons, *** p < 0.0005. B Tube test of social dominance at 16 months of age (16MO) displaying the total head-to-head battles and win percentage by genotype comparing wild type against K408R (K408R/ + and K408R/K408R animals). Binomial Test of Observed vs. Expected with Expected due to random chance set to 50%, * p < 0.05. C Quantification of total distance traveled (cm) and total time in center (s) in the open field test of female mice. Mixed Effects Analysis with Tukey’s multiple comparison data presented as mean ± SEM, *** p < 0.0005, * p < 0.05. D Quantification of percent alternations in the spontaneous Y-maze test of female mice at 2, 9, and 16 months of age (2MO, 9MO, 16MO, respectively). Mixed-Effects Analysis with Tukey’s multiple comparison data presented as mean ± SEM, * p < 0.05. E Quantification of relative ambulatory activity normalized to wild type at 1 h of female mice at 2, 9, and 16 months of age (2MO, 9MO, and 16MO, respectively). Grey shading between hours 2 and 14 indicate “lights off” with respect to day/night light cycle. 2-Way ANOVA with Tukey’s multiple comparison data presented as mean ± SEM, * p < 0.05. All assays present wild type mice in grey and K408R/K408R mice in purple