Figure 2. Genetic reduction and normalization of Gdf11 dose ameliorates several behavioral deficits in MECP2-TG1 mice.

Behavioral characterization of MECP2-TG1, MECP2-TG1; Gdf11^tm2b/+ double mutants, and their respective wild-type littermate controls was performed beginning at 16 weeks of age. (A) Open-field assessment of locomotion and activity. (B) Elevated plus maze assay measures of movement and anxiety-like behaviors. (C) Learning assessment using contextual fear-conditioning. Greater freezing indicates better memory of the context. Central estimate of data is shown as mean ± sem. Closed circles denote male mouse data points and open circles denote female mouse data points. For all open field and elevated plus maze (A,B), n=30 wild-type mice (19 male, 11 female); n=26 MECP2-TG1 mice (14 male, 12 female); and n=22 MECP2-TG1; Gdf11^tm2b/+ mice (16 male, 6 female). For fear conditioning assay (C), n=17 wild-type mice (9 male, 8 female); n=25 MECP2-TG1 mice (13 male, 12 female); and n=22 MECP2-TG1; Gdf11^tm2b/+ mice (16 male, 6 female). All data were analyzed using a Welsch one-way ANOVA with Dunnett’s post hoc multiple comparisons, and raw measurements are provided in Figure 2—source data 1. * p<0.05, ** p<0.01, *** p<0.001, and **** p<0.0001.

Figure 2—figure supplement 1. Correction of Gdf11 dose does not ameliorate all behavioral deficits in MECP2-TG1 mice.

Behavioral characterization of MECP2-TG1, MECP2-TG1; Gdf11^tm2b/+ double mutants, and their respective wild-type littermate controls was performed beginning at 16 weeks of age. (A) Timeline and order of behavioral assays. (B) Open-field assessment of anxiety-like behavior as measured by entries into the center of the arena, ratio of the distance traveled in the center to total, and ratio of the time spent in the center over total. (C) Learning assessment during training and cued fear-conditioning. Greater freezing indicates better memory of the cue. (D) Motor coordination measured by the rotating rod assay. (E) Locomotion and anxiety-like behaviors measured by the light-dark assay. Mice with anxiety-like behaviors prefer to spend longer duration in the dark segment of the arena. (F, G) Sociability measured by the three-chamber assay, split into acclimation phase (F) and social phase (G). Central estimate of data is shown as mean ± sem. Closed circles denote male mouse data points and open circles denote female mouse data points. For all assays except fear conditioning, n=30 wild-type mice (19 male, 11 female); n=26 MECP2-TG1 mice (14 male, 12 female); and n=22 MECP2-TG1; Gdf11^tm2b/+ mice (16 male, 6 female). For fear conditioning assay (C), n=17 wild-type mice (9 male, 8 female); n=25 MECP2-TG1 mice (13 male, 12 female); and n=22 MECP2-TG1; Gdf11^tm2b/+ mice (16 male, 6 female). All data were analyzed using a Welsch one way ANOVA with Dunnett’s post hoc multiple comparisons, and raw measurements are provided in Figure 2—source data 1. * p<0.05, ** p<0.01, *** p<0.001, and **** p<0.0001.