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. 2022 Apr 13;31(17):2964–2988. doi: 10.1093/hmg/ddac087

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© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

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Altered social behavior in Scn2a^E/+ mice. (A) Sociability phase of three-chamber assay. Amount of time spent sniffing either an empty cup (EC) or unfamiliar mouse (S1) in Scn2a^E/+ mice compared with WT at 10 weeks of age. Two-way ANOVA (using target as a within-subject variable) comparing average sniffing time between Scn2a^E/+ and WT males showed a significant main effect of target [F(1,24) = 57.28, P < 0.0001] and a significant interaction between target and genotype [F(1,24) = 9.198, P = 0.0057]. Both Scn2a^E/+ and WT males spent significantly more time sniffing an unfamiliar mouse compared with an empty cup (Scn2a^E/+: ^****P < 0.0001, WT: ^**P = 0.0100; Sidak’s post-hoc test). However, Scn2a^E/+ males spent significantly more time sniffing an unfamiliar mouse compared with WT males (WT: 93.3 ± 12.7 s, Scn2a^E/+: 132.6 ± 8.3 s, ^**P = 0.0024; Sidak’s post-hoc test). Two-way ANOVA comparing average sniffing time between Scn2a^E/+ and WT females showed a significant main effect of target only [F(1,22) = 35.17, P < 0.0001]. Both Scn2a^E/+ and WT females spent significantly more time sniffing an unfamiliar mouse compared with an empty cup (Scn2a^E/+: ^***P < 0.0007, WT: ^***P < 0.0008; Sidak’s post-hoc test). (B) Social novelty phase of three-chamber assay. Amount of time spent sniffing either a familiar mouse (S1) or an unfamiliar mouse (S2) in Scn2a^E/+ mice compared with WT at 10 weeks of age. Two-way ANOVA (using target as a within-subject variable) comparing average sniffing time between Scn2a^E/+ and WT males showed significant main effects of target [F(1,26) = 19.02, P = 0.0002] and genotype [F(1,21) = 11.85, P = 0.0020]. Both Scn2a^E/+ and WT males spent significantly more time sniffing an unfamiliar mouse compared with a familiar mouse (Scn2a^E/+: ^**P = 0.0019, WT: ^*P = 0.0432; Sidak’s post-hoc test). However, Scn2a^E/+ males spent significantly more time sniffing an unfamiliar mouse compared with WT males (WT: 48.5 ± 8.7 s, Scn2a^E/+: 77.1 ± 5.7.3 s, ^**P = 0.0042; Sidak’s post-hoc test). Two-way ANOVA comparing average sniffing time between Scn2a^E/+ and WT females also showed significant main effects of target [F(1,22) = 9.145, P = 0.0062] and genotype [F(1,22) = 6.081, P = 0.0219]. However, only Scn2a^E/+ females spent significantly more time sniffing an unfamiliar mouse compared with a familiar mouse (Scn2a^E/+: ^*P = 0.0327, WT: P = 0.1889; Sidak’s post-hoc test). Symbols represent individual mice, horizontal lines represent mean and error bars represent SEM. Males and females were analyzed separately, with n = 12–14 per genotype for males and n = 11–13 per genotype for females.