Assessing autism-like behavior in mice: variations in social interactions among inbred strains

Abstract

Autism is a pervasive developmental disorder, with characteristics including impairments in reciprocal social interaction, impaired communication, and repetitive/stereotyped behaviors. Despite decades of research, the etiology of autism remains elusive. Thus, it is important that we pursue all avenues, in attempting to understand this complicated disorder. One such avenue is the development of animal models. While autism may be uniquely human, there are behavioral characteristics of the disorder that can be established in animal models. Evidence supports a genetic component for this disorder, and over the past few decades the mouse has been a highly valuable tool for the elucidation of pathways involved in many human disorders (e.g., Huntington's disease). As a first step toward establishing a mouse model of autism, we studied same-sex social behavior in a number of inbred mouse strains. In Study 1, we examined intra-strain social behavior of male pairs after one mouse had 15 min prior exposure to the testing chamber. In Study 2, we evaluated intra-strain and inter-strain social behavior when both mice were naive to the testing chamber. The amount and type of social behavior seen differed between these studies, but overall there were general inbred strain differences in social behavior. Some strains were highly social, e.g., FVB/NJ, while others displayed low levels of social behavior (e.g., A/J, BTBR T+tf/J). These strains may be useful in future genetic studies to determine specific genes involved in mouse social behavior, the findings of which should in turn help us to determine some of the genes involved in human social behavior and its disorders (e.g., autism).

Figure 1

Intra-strain social interaction, when one mouse of the pair had prior experience in the testing chamber. Mean (± SEM) time spent engaged in any type of social interaction (12 pairs per strain of 129S1, B6, BTBR, D2, and FVB) during the 20-minute session.

Figure 2

Intra-strain and inter-strain social interaction, when both mice of a pair were naïve to the testing chamber. Mean (± SEM) time spent engaged in any type of social interaction (12 pairs per strain of 129S1, A, B6, BTBR, CBy, D2, and FVB, and 12 BTBR-FVB pairs) during the 30-minute session.

Figure 3

Mean (± SEM) time spent engaged in sniffing behavior (12 pairs per strain of 129S1, A, B6, BTBR, CBy, D2, and FVB, and 12 BTBR-FVB pairs) when both mice of a pair were naïve to the testing chamber during the 30-minute session.

Figure 4

Intra-strain and inter-strain social interaction, when both mice of a pair were naïve to the testing chamber. Mean (± SEM) time spent engaged in positive social behaviors (e.g., huddling, allogrooming) (12 pairs per strain, 129S1, A, B6, BTBR, CBy, D2, and FVB, and 12 BTBR-FVB pairs) during the 30-minute session.

Figure 5

Effects of pairing male mice from inbred strains with high and low levels of social interaction behavior (12 pairs BTBR-BTBR, BTBR-FVB, FVB-FVB). Mean (± SEM) time spent engaged in negative social behavior (e.g., wrestling and biting) during the 30-minute session.