Male and Female Mice Lacking Neuroligin-3 Modify the Behavior of Their Wild-Type Littermates

Abstract

In most mammals, including humans, the postnatal acquisition of normal social and nonsocial behavior critically depends on interactions with peers. Here we explore the possibility that mixed-group housing of mice carrying a deletion of <i>Nlgn3</i>, a gene associated with autism spectrum disorders, and their wild-type littermates induces changes in each other's behavior. We have found that, when raised together, male <i>Nlgn3</i> knockout mice and their wild-type littermates displayed deficits in sociability. Moreover, social submission in adult male <i>Nlgn3</i> knockout mice correlated with an increase in their anxiety. Re-expression of <i>Nlgn3</i> in parvalbumin-expressing cells in transgenic animals rescued their social behavior and alleviated the phenotype of their wild-type littermates, further indicating that the social behavior of <i>Nlgn3</i> knockout mice has a direct and measurable impact on wild-type animals' behavior. Finally, we showed that, unlike male mice, female mice lacking <i>Nlgn3</i> were insensitive to their peers' behavior but modified the social behavior of their littermates. Altogether, our findings show that the environment is a critical factor in the development of behavioral phenotypes in transgenic and wild-type mice. In addition, these results reveal that the social environment has a sexually dimorphic effect on the behavior of mice lacking <i>Nlgn3</i>, being more influential in males than females.