Fig. 3: NEXMIF restoration rescues social novelty preference in adolescent KO mice.

A Paradigm for the Three-Chamber Social Test. During the two-day habituation phase (left panel), the test mouse was released from the center chamber, with empty cages in either of the side chambers, and allowed to move freely within the environment for 5 min. During the sociability test on the third day (middle panel), an unfamiliar mouse (Mouse 1) was placed into either of the side chambers and the test mouse was allowed to move freely within the environment for 5 min. During the social novelty test (right panel), a second mouse (Novel Mouse) was placed into the remaining empty chamber and the test mouse was allowed to interact with both mice for 5 min. B Traces of mouse track paths on the first day of habituation for WT + CTRL, KO + CTRL, and KO + NEX mice. C Traces of mouse track paths in the sociability test for WT + CTRL, KO + CTRL, and KO + NEX mice. The star indicates the location of Mouse 1. D Traces of mouse track paths in the social novelty test for WT + CTRL, KO + CTRL, and KO + NEX mice. The star indicates the location of the Novel Mouse. E Quantification of the exploration time during habituation revealed no preference for either side chamber within each group of injected mice (n = 8 WT + CTRL, 6 KO + CTRL, 6 KO + NEX). F Quantification of the Sociability Preference Index (PI): KO + CTRL mice showed a reduced social PI for Mouse 1, while KO + NEX mice trended towards an increased social PI for Mouse 1. G Quantification of the Social Novelty PI: KO + CTRL mice displayed an attenuated social PI for the novel mouse, which was rescued by ICV injection of LV-NEXMIF in the KO + NEX mice. Data are represented as average ± SEM. Two-way ANOVA with Sidak’s multiple comparisons test (E) or One-way ANOVA with Tukey’s multiple comparisons test (F-G). *p < 0.05; ***p < 0.001; ns, Not significant.