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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

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Altered anxiety-related behavior and rotarod performance in Scn2a^E/+ mice. (A) Percent time spent in the open arms of a zero-maze apparatus in Scn2a^E/+ mice compared with WT at 6 weeks of age. Scn2a^E/+ males spent significantly more time in the open arms compared with WT (WT: 15.3 ± 2.2%, Scn2a^E/+: 30.5 ± 4.1%, ^**P = 0.0023; Student’s t-test). Scn2a^E/+ females spent significantly more time in the open arms compared with WT (WT: 22.0 ± 2.0%, Scn2a^E/+: 34.8 ± 4.9%, ^*P = 0.0297; Welch’s t-test). (B) Percent time spent in the light zone of a light/dark box in Scn2a^E/+ mice compared with WT at 7 weeks of age. Scn2a^E/+ males spent significantly more time in the light zone compared with WT (WT: 20.9 ± 2.0%, Scn2a^E/+: 29.2 ± 3.2%, ^*P = 0.0367; Student’s t-test). Scn2a^E/+ females also spent significantly more time in the light zone compared with WT (WT: 21.1 ± 1.7%, Scn2a^E/+: 32.1 ± 3.5%, ^*P = 0.0367; Mann–Whitney test). (C) Percent time spent in the center zone of an open field apparatus in Scn2a^E/+ mice compared with WT at 8 weeks of age. There was not a significant difference in the amount of time spent in the center zone between Scn2a^E/+ and WT males (P = 0.0556, Mann–Whitney test). However, Scn2a^E/+ females spent significantly more time in the center zone compared with WT (WT: 6.27 ± 0.9%, Scn2a^E/+: 10.1 ± 1.2%, ^*P = 0.0167; Mann–Whitney test). (D) Number of marbles buried during a 30-min trial by Scn2a^E/+ mice compared with WT at 6 weeks of age is displayed. Scn2a^E/+ males buried significantly fewer marbles compared with WT (WT: 12 ± 1, Scn2a^E/+: 5 ± 2, ^**P = 0.0019; Mann–Whitney test). Scn2a^E/+ females also buried significantly fewer marbles compared with WT (WT: 13 ± 2, Scn2a^E/+: 2 ± 1, ^****P = 0.0001; Mann–Whitney test). (E) Average latency to fall during an accelerating rotarod task measured on three consecutive days in Scn2a^E/+ mice compared with WT at 9 weeks of age. Daily performance for each animal was assessed by averaging across three trials. Two-way repeated measures ANOVA comparing average latency to fall between Scn2a^E/+ and WT males showed significant main effects of test day [F(1.511, 34.76) = 8.450, ^**P = 0.0022] and genotype [F(1,23) = 10.18, ^*P = 0.0041]. Scn2a^E/+ males took significantly longer to fall compared with WT on day 3 (WT: 121 ± 6 s, Scn2a^E/+: 152 ± 7 s, P = 0.0106; Sidak’s post-hoc test). Two-way repeated measures ANOVA comparing average latency to fall between Scn2a^E/+ and WT females showed a significant main effect of test day only [F(1.594,36.65) = 6.646, ^**P = 0.0059]. For panels (A–D) symbols represent individual mice, horizontal lines represent mean and error bars represent SEM. For panel (E) symbols and error bars represent mean ± SEM. Males and females were analyzed separately, with n = 12–14 per genotype for males and n = 11–15 per genotype for females.