Fig. 2: Adult IRSp53 re-expression rescues direct social interaction and social approach in IRSp53-cKO mice.

a Experimental scheme showing injection of PHP.eB-IRSp53 or control (PHP.eB-EGFP) into the retro-orbital sinus of WT or IRSp53-cKO mice at postnatal week 8 and performance of behavioral tests (direct social interaction and three-chamber test) at postnatal week ~12. b PHP.eB-IRSp53 injection rescues social interaction in IRSp53-cKO mice in the direct social-interaction test, as shown by nose-to-nose interaction (but not by body contact time), without affecting direct social interaction in WT mice. Mouse pairs of the same genotype (WT or cKO) were used (n = 7 mice [WT-EGFP], 13 [WT-IRSp53], 6 [IRSp53-cKO-EGFP], and 7 [IRSp53-cKO-IRSp53], two-way ANOVA with Sidak’s test). c–f PHP.eB-IRSp53 injection rescues social approach in IRSp53-cKO mice, but not in WT mice, in the three-chamber test, as shown by time spent sniffing stranger 1 (S1) and object (O). Note that the effect of PHP.eB-IRSp53 injection on social novelty recognition (S1 vs. new stranger (S2)) in IRSp53-cKO mice could not be determined because WT mice expressing EGFP (positive control) did not show a baseline preference for S2 over S1 (n = 11 mice [WT-EGFP], 13 [WT-IRSp53], 9 [IRSp53-cKO-EGFP], and 11 [IRSp53-cKO-IRSp53] for social approach, 11 mice [WT-EGFP], 11 [WT-IRSp53], 7 [IRSp53-cKO-EGFP], and 10 [IRSp53-cKO-IRSp53] for social novelty, two-way ANOVA [for group × target interactions where group means the four groups [WT-EGFP/IRSp53 and IRSp53-cKO-EGFP/IRSp53] and target means the two targets [S1/O]], Wilcoxon/Student’s t-test [for the comparison of two different targets [S1 vs. O; S1 vs. S2] within each group [i.e., WT-EGFP], specific p values for S1 vs. S2 for each group: 0.3652 [WT-EGFP], 0.7220 [WT-IRSp53], 0.6963 [cKO-EGFP], and 0.8457 [cKO-IRSp53] (see Supplementary Data 1 for further details). Significance values are indicated as *p < 0.05, **p < 0.01, ***p < 0.001, or ns (not significant, p > 0.05). Error bars represent the standard errors of means.