Figure 3

Behavioral phenotype. Automated recording of locomotion increased activity of hom E8 animals at the age of 10 months (A); gray bars indicate dark phases; dots show circadian pattern of cumulative distance moved; data were analyzed by two-way ANOVA for repeated measurements followed by Bonferroni’s post hoc test (factor genotype, * p = 0.032) and represent means ± SEM; n ≥ 4 animals per genotype. This hyperactivity was confirmed in het/het E85 mice at the age of 6 months (B); data were analyzed by two-way ANOVA for repeated measurements followed by Bonferroni’s post hoc test (factor genotype, * p = 0.012) and represent means ± SEM; n = 12 animals per genotype. At the age of 8 months in het/het E85 mice, the significantly increased activity is already detectable after 44 h of measurement (C); data were analyzed by two-way ANOVA for repeated measurements followed by Bonferroni’s post hoc test (factor genotype, * p = 0.017) and represent means ± SEM; n ≥ 10 animals per genotype. Monthly primary screening revealed a progressive decrease of reactivity on a given acoustic signal, affecting ~90% hom E8 animals at the age of 6 months (D); bars show percentage of affected animals; n ≥ 7 animals per genotype; only males were used. In het/het E85 animals this behavioral phenotype was delayed, affecting ~90% at the age of 10 months (E); bars show percentage of affected animals; n ≥ 22 animals per genotype. Analysis of het/het E85 animals at the age of 7 months, revealed a decrease of PPI of the auditory startle reflex across 72–84 dB prepulse intensity (F); data were analyzed by two-way repeated-measures ANOVA followed by Bonferroni’s post-hoc test and represent means ± SEM; *** p < 0.001 n = 9–10 animals per genotype.