Social propinquity in rodents as measured by tube cooccupancy differs between inbred and outbred genotypes

Significance We developed an assay of social behavior, the tube cooccupancy test. This assay is able to identify deficits in social behavior of known “autistic-like” mouse strains. Using the test, we revealed a major difference in social behavior between inbred and outbred strains, with only the latter behaving similar to wild mice. Existing assays of social interaction are suboptimal, and none measures propinquity, the tendency of rodents to maintain close physical proximity. These assays are ubiquitously performed using inbred mouse strains and mutations placed on inbred genetic backgrounds. We developed the automatable tube cooccupancy test (TCOT) based on propinquity, the tendency of freely mobile rodents to maintain close physical proximity, and assessed TCOT behavior on a variety of genotypes and social and environmental conditions. In outbred mice and rats, familiarity determined willingness to cooccupy the tube, with siblings and/or cagemates of both sexes exhibiting higher cooccupancy behavior than strangers. Subsequent testing using multiple genotypes revealed that inbred strain siblings do not cooccupy at higher rates than strangers, in marked contrast to both outbred and rederived wild mice. Mutant mouse strains with “autistic-like” phenotypes (Fmr1−/y and Eif4e Ser209Ala) displayed significantly decreased cooccupancy.

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