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. 2024 Apr 29;121(19):e2307156121. doi: 10.1073/pnas.2307156121

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Copyright © 2024 the Author(s). Published by PNAS.

This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).

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Fig. 3. — Mutant mice display improved rotarod performance with enhanced rearing and grooming in the open field. (A) Celsr3^C1906Y/+ males/females and Celsr3^S1894Rfs*2/+ males perform better on an accelerating rotarod. Wwc1^W88C/+ mice show normal latency to fall. (B) Celsr3^C1906Y/+ females travel more distance in the open field. Celsr3^C1906Y/+ males show a trend-level effect (P = 0.09). Celsr3^S1894Rfs*2/+ male and female mice travel similar distances in the open field compared to wild-type littermates. Wwc1^W88C/+ males travel more distance in the open field but females travel similar distance. (C, Top Panel) Celsr3 males and females rear more in the open field. Rearing events trended up for Wwc1^W88C/+ males (P = 0.066) but not females. (Bottom Panel) Time spent rearing within separate binned 10-min intervals. (D) Aripiprazole pretreatment attenuates rearing behavior. Wild-type/Celsr3^C1906Y/+: [F(11, 114) = 17.99, P < 0.00001, R² = 0.59], genotype (P < 0.0001), treatment (P < 0.0001), genotype (x) treatment interaction (P = 0.291); wild-type/Celsr3^S1894Rfs*2/+: [F(11, 117) = 18.13, P < 0.00001, R² = 0.59], genotype (P < 0.0001), treatment (P < 0.0001), genotype (x) treatment interaction (P = 0.269). (E) Celsr3^C1906Y/+ females groom more in the open field and males show a trend. Celsr3^S1894Rfs*2/+ females and males also groom more. Wwc1^W88C/+ mice show no differences. (A–C) RM Two-way RM ANOVA, main effect genotype with Bonferonni’s Multiple Comparisons Test. (A) Celsr3^+/+/Celsr3^C1906Y/+ female (n = 20/14), male n = 17/15; Celsr3^+/+/Celsr3^S1894Rfs*2/+ female (n = 20/18), male (n = 17/29); Wwc1^+/+/Wwc1^W88C/+ female (n = 16/31), male (n = 19/40). (B and C) Celsr3^+/+/Celsr3^C1906Y/+ female (n = 16/16), male n = 15/17; Celsr3^+/+/Celsr3^S1894Rfs*2/+ female (n = 18/25), male (n = 12/29); Wwc1^+/+/Wwc1^W88C/+ female (n = 12/21), male (n = 13/18). (D) Multiple linear regression (factor III) with Tukey’s post hoc test. Vehicle-WT/Celsr3^C1906Y/+ (n = 12/10), Drug-WT/Celsr3^C1906Y/+ (n = 10/10); Vehicle-WT/Celsr3^S1894Rfs*2/+ (n = 12/11), Drug-WT/Celsr3^S1894Rfs*2/+ (n = 10/10). (E) Mann–Whitney U test. Celsr3^+/+/Celsr3^C1906Y/+ female (n = 13/12), male (n = 10/18); Celsr3^+/+/Celsr3^S1894Rfs*2/+ female (n = 14/21), male (n = 12/17); Wwc1^+/+/Wwc1^W88C/+ female (n = 11/16), male (n = 11/29) *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001; ^#P < 0.05, ^##P < 0.01. Full description of statistics in SI Appendix, Table S1.