Male and female mice lacking Neuroligin-3 modify the behavior of their wild-type littermates

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