Fig. 2

Early developmental downregulation of microglial Fmr1 causes sex-specific behavioural alterations (A) Schematic illustration of early deletion of Fmr1 gene in microglia. (B– F) Behavioral analysis of female Fmr1 cKOearly (KO n = 7, Control n = 10) showed that the mice spend less time in the inner zone and more time in the outer zone of the open field test (B, inner zone time: t15 = 2.20, *p = 0.0438 and outer zone time: t15 = 2.20, *p = 0.043). Female Fmr1 cKOearly mice spent more time self-grooming (C, t15 = 2.44, *p = 0.0273 ) and buried more marbles (D, **p = 0.0068). No anxiety-like behavior was observed in the elevated plus maze (E, ns, p > 0.05). In the three-chamber social interaction test, female Fmr1 cKOearly mice exhibited impaired novelty seeking (F, left: ns, p > 0.05), whereas no impairment was observed in the sociability phase of the test (F, right: t30 = 5.67, ****p < 0.0001). (G– K) No significant differences in male Fmr1 cKOearly mice as compared to controls in the open field, self-grooming, marble burying, elevated plus maze, and three-chamber social interaction tests (G– K, ns, p > 0.05 for all tests, n = 8–9). Unpaired two-tailed Student’s t-test was used for B-C, E, and G-I, and two-tailed Mann–Whitney test was used for D and J. 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 < 0.05, **p < 0.01, ****p < 0.0001, ns– not significant