Expression of social behaviors of C57BL/6J versus BTBR inbred mouse strains in the visible burrow system

Abstract

The core symptoms of autism spectrum disorder (ASD) include deficits in social interaction, impaired communication, and repetitive behaviors with restricted interests. Mouse models with behavioral phenotypes relevant to these core symptoms offer an experimental approach to advance the investigation of genes associated with ASD. Previous findings demonstrate that BTBR T+ tf/J (BTBR) is an inbred mouse strain that shows robust behavioral phenotypes with analogies to all three of the diagnostic symptoms of ASD. In the present study, we investigated the expression of social behaviors in a semi-natural visible burrow system (VBS), during colony formation and maintenance in groups comprising three adult male mice of the same strain, either C57BL/6J (B6) or BTBR. For comparative purposes, an extensively investigated three-chambered test was subsequently used to assess social approach in both strains. The effects of strain on these two situations were consistent and highly significant. In the VBS, BTBR mice showed reductions in all interactive behaviors: approach (front and back), flight, chase/follow, allo-grooming and huddling, along with increases in self-grooming and alone, as compared to B6. These results were corroborated in the three-chambered test: in contrast to B6, male BTBR mice failed to spend more time in the side of the test box containing the unfamiliar CD-1 mouse. Overall, the present data indicates that the strain profile for BTBR mice, including consistent social deficits and high levels of repetitive self-grooming, models multiple components of the ASD phenotype.

Fig. 1

Three-chambered apparatus. Three interconnected chambers are separated by two manually operated sliding doors. Side compartments contain inverted wire cups to house a stimulus mouse. A steel weight and a clear Plexiglas cylinder are placed above the inverted cups to prevent lifting or climbing on top. The inset displays a front view demonstrating the clear Plexiglas window on the front of the apparatus.

Fig. 2

Individual frequencies (mean ± S.E.M.) of approaches to the front and approaches to the back of C57BL/6J and BTBR mice during the dark and light periods in the VBS. *Indicates significant differences between both strains; p<0.05; n=12 for each group.

Fig. 3

Individual frequencies (mean ± S.E.M.) of flight (upper panel) and chase/follow (lower panel) behaviors of C57BL/6J and BTBR mice during the dark and light periods in the VBS. *Indicates significant differences between both strains; p<0.05; n=12 for each group.

Fig. 4

Individual frequencies (mean ± S.E.M.) of self-grooming (upper panel) and allo-grooming (lower panel) behaviors of C57BL/6J and BTBR mice during the dark and light periods in the VBS. *Indicates significant differences between both strains; p<0.05; n=12 for each group.

Fig. 5

Percentage of observation (mean ± S.E.M.) verified for each huddle (upper panel) or being alone (lower panel) of C57BL/6J and BTBR mice during the dark and light periods in the VBS. *Indicates significant differences between both strains; p<0.05; n=12 for each group.

Fig. 6

Time spent in each side (mean ± S.E.M.) during the three-chambered social approach test. *p<0.05, within-strain comparison; n=12 for each group.