Figure 2. Sex effects on behavior in Gnptab^−/− and Gnptg^−/− mice.

(A) In addition to a significant genotype effect, an ANOVA conducted on the ledge data from the Gnptab^−/− and WT control mice at 1 month of age revealed a significant sex effect (p  =  0.025) and a genotype x sex interaction (p  =  0.041). Subsequent contrasts showed that male Gnptab^−/− mice were significantly impaired on the ledge test compared to the male WT mice [F(1,23)  =  12.98, *p  =  0.002], while differences were not significant between the female groups. (B) Analysis of the 60° inclined screen data from the 4-6 month old Gnptg^−/− mice showed a significant genotype x sex interaction (p  =  0.041) in addition to the significant genotype effect, suggesting that impaired performance may have varied differentially as a function of sex in each group. Additional contrasts documented that the male Gnptg^−/− mice took significantly longer to reach the top of the apparatus compared to the males from the WT group [F(1,16)  =  21.51, *p  =  0.0003), while the performance of the females from the two groups did not differ significantly. (C) An rmANOVA on the stationary rod data from testing the Gnptg^−/− and control mice at 4–6 months of age revealed a significant sex x trials interaction, (**p  =  0.030) as well as a significant (*) genotype effect and a significant (***) genotype x trials interaction, suggesting that differences in performance were dependent on trials and sex. Additional contrasts showed that the performance of the male groups of mice did not differ across the stationary rod trials, although the female Gnptg^−/− mice were significantly impaired compared to the WT controls, [F(1,16)  =  6.72, p  =  0.020), with significant differences being observed on the first trial (††p  =  0.004). (D) Robust performance impairments in the Gnptg^−/− mice at 4-6 months of age were observed during the accelerating rotarod test where an rmANOVA yielded a significant genotype x sex x trials interaction, (***p  =  0.004), along with a significant (*) genotype effect and significant (**) genotype x sessions interaction. Subsequent contrasts relating to the sex effect showed that the male Gnptg^−/− mice remained on the rod longer than the male control group [F(1,16)  =  5.64, p  =  0.031) with significant differences occurring on session 3 - trial 1 (†p  =  0.002), although large differences were also found for session 1 - trial 2 (#p  =  0.036) and session 2 - trial 1 (#p  =  0.039). Differences were even greater in the female groups whereby the female Gnptg^−/− mice performed significantly worse than the control females [F(1,16)  =  17.65, p  =  0.0007), with significant differences being observed for session 1 - trial 2 (††p  =  0.0007), session 2 - trial 2 (††p  =  0.0004), session 3 - trial 1 (††p  =  0.0002), and session 3 - trial 2 (††p  =  0.002). (E) Analysis of the accelerating rotarod data at 12–14 months revealed a significant genotype x gender x trials x sessions interaction, (**p  =  0.017), as well as a significant (*) genotype effect. Additional contrasts related to the sex variable showed that the female Gnptg^−/− mice exhibited significantly inferior performance on average across trials and sessions compared to the female WT group [F(1,15)  =  25.37, p  =  0.0001). Pair-wise comparisons revealed significant differences between the female groups on every trial (††p <0.007) except session 1 - trial 1 (##p  =  0.016), where differences were also very large. The performance of the male Gnptg^−/− mice was also significantly compromised relative to the male WT controls on average across trials and sessions, although the differences were smaller [F(1,15)  =  6.48, p  =  0.022). Pair-wise comparisons showed that the performance of the male groups differed significantly on session 2 - trial 2 (†p  =  0.006), although large differences were also observed on session 1 - trial 2 (#p  =  0.049), and session 3 - trial 2 (#p  =  0.041).