Fig. 4
Microglia-specific downregulation of Fmr1 during late development leads to a deficit in novelty-seeking phase of the three-chamber social interaction test in female mice. (A) The schematic illustrates the late downregulation of the Fmr1 gene in microglia. (B– F) The behavioral analysis of female Fmr1 cKOlate mice (n = 9) revealed impairment during novelty-seeking phase of the three-chamber social interaction test (F, right, ns, p > 0.05 ), but not during the sociability phase of the same test (F, left, t36 = 10.31, ****p < 0.0001). The female Fmr1 cKOlate mice behaviors in the open field, self-grooming, marble burying, and elevated plus tests were comparable to the controls (B– E, ns, p > 0.05). The male Fmr1 cKOlate mice did not show behavioral deficit during the open field, self-grooming, marble burying, and elevated plus tests in comparison to controls (G– J, ns, p > 0.05). The male Fmr1 cKOlate mice did not exhibit impairment in sociability or novelty-seeking phases of the three-chamber social interaction test (K, ****p < 0.0001 and ***p < 0.0001 for empty cage (E) vs. stranger 1 (S1) and stranger 2 (S2) vs. stranger 1 (S1) in control and male Fmr1 cKOlate). Unpaired two-tailed Student’s t-test was used for D, and G-J. Two-tailed Mann–Whitney test was used for B, C, and E. The three-chamber social interaction test was analyzed using two-way ANOVA followed by Bonferroni’s multiple comparisons test. Data points represent individual mice. Data are shown as mean ± SEM. **p < 0.01, ***p < 0.001, ****p < 0.0001, ns– not significant