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. 2018 Mar 12;141(5):1350–1374. doi: 10.1093/brain/awy046

Figure 4.

Figure 4

Generation, genomic analysis, routine behavioural observation and spontaneous activity of Stxbp1+/− mice. (A–D) Generations of four lines of Stxbp1+/− mice: conditional, congenic BL6, reverse 129Sv and Gad2- Stxbp1 line. Chromosomes bearing Stxbp1 mutation originating from the C57BL/6J genetic background are shown in grey, and those from the 129/SvJ genetic background are shown in orange. Stxbp1 mutation is represented with grey triangle; LoxP sites are represented with black rectangles and Cre-deleter lines are represented with scissors (red scissors: Cre expressed in all neuron, blue scissors: Gad2tm2-Cre mice with Cre-recombinase expressed in only GABAergic neurons). The flanking gene region is represented as orange region in the grey chromosome in the congenic BL6 line and vice versa in the reverse 129Sv line (adapted from Wolfer et al., 2002). (E and F) High-density genomic analysis showed the size and position of flanking gene region in Stxbp1+/− samples from congenic BL6 and reverse 129Sv lines. ‘Me-PaMuFind-It’ web tool (http://me-pamufind-it.org/) revealed three genes with passenger mutations from 129Sv genetic background within flanking genes region in congenic BL6 Stxbp1+/− samples. (G) Stxbp1+/− mice showed lower body weight compared to their controls. (H) Grip strength was normal in Stxbp1+/− mice. (I) Motor coordination and motor learning in Stxbp1+/− mice was normal, as assessed on the rotarod. (J and K) Circadian rhythm assessed by changes in the activity in anticipation of (filled bars), and response to (open bars), day/night transitions and proportion of time spent outside the shelter was normal in Stxbp1+/− mice. (L) Proportion of activity duration during the first 3 h of the dark phase days in the home-cage environment (PhenoTyper) showed increased activity of Stxbp1+/− mice from all three lines during the first dark phase. (M) Proportion of activity duration in the PhenoTyper during the light phases was overall lower for Stxbp1+/− mice (conditional mice, congenic BL6 and reverse 129Sv). The number of animals assigned is shown in the graphs. *P < 0.05; ***P < 0.001.