Fig. 3: Molecular and behavioral characterization of heterozygous Disc1 KI mice carrying the 4-bp deletion mutation of the Disc1 gene.

a Protein expression levels in cortical and hippocampal lysates of 4-month-old WT and KI mice. KI refers to heterozygous Disc1 mutant mice. Shown are sample western blot images and quantification of protein levels of DISC1, SV2, PDE4A, and PDE4B. Data were normalized to β-actin for sample loading and then to WT in the same blot for comparison. Values represent mean ± s.e.m. (DISC1: n = 6; SV2: n = 2; PDE4A: n = 4; PDE4B: n = 6 independent experiments for cortex; DISC1: n = 5; SV2: n = 8; PDE4A: n = 6; PDE4B: n = 5 independent experiments for hippocampus; One-way ANOVA with p values indicated). b Impaired paired-pulse ratio in Disc1 KI mice. The electrophysiological response of CA1 neurons to paired pulses of stimulation of CA3 neurons from acutely prepared hippocampal slices. The paired pulses were separated by intervals of 25, 50, 75, and 100 ms. Values represent mean ± s.e.m. (n = 14 for WT and n = 20 for KI; One-way ANOVA with p values indicated). c Basal anxiety of Disc1 KI mice in the elevated plus-maze test. The percentage of time spent in the open arm over total time was calculated. Values represent mean ± s.e.m. (n = 12 for WT and n = 5 for KI, 13-week-old male littermates; One-way ANOVA with p values indicated). d Three-chamber social preference test showing impaired social novelty recognition of Disc1 KI mice (right), but normal general sociability (left). Time spent in each chamber was calculated. Values represent mean ± s.e.m. (n = 16 for WT and n = 11 for KI, 16-week-old male littermates; One-way ANOVA with p values indicated). e Disc1 KI mice showed a higher level of D-amphetamine (Amph)-induced hyperactivity. Locomotor activity was measured 60 min before and 120 min immediately after Amph treatment. A total number of beam breaks was measured. Data are shown in 5 min intervals. Values represent mean ± s.e.m. (n = 9 for WT and n = 18 for KI, 16-week-old male littermates; One-way ANOVA with p values indicated). f Impaired spatial working memory of Disc1 KI mice in the Y-maze task. The time spent in each arm during the 5 min test was shown. Values represent mean ± s.e.m. (n = 10 for WT and n = 11 for KI, 14-week-old male littermates; One-way ANOVA with p values indicated). g Impaired spontaneous alternation of Disc1 KI mice in the T-maze task. The percentage of alternations (alternated arm entry on two consecutive trials) was scored for 15 trials. Values represent mean ± s.e.m. (n = 21 for WT and n = 15 for KI, 18-week-old male littermates; One-way ANOVA with p values indicated). h Decrease of discriminative activity of Disc1 KI mice in the novel object recognition test. KI mice showed no preference for the novel object over the familiar object. Values represent mean ± s.e.m. (n = 7 for WT and n = 8 for KI, 15-week-old male littermates; One-way ANOVA with p values indicated). Source data are provided as a Source Data file.