Decreased aggression and increased repetitive behavior in Pten haploinsufficient mice.

Abstract

Aggression is an aspect of social behavior that can be elevated in some individuals with autism spectrum disorder (ASD) and a concern for peers and caregivers. Mutations in Phosphatase and tensin homolog (PTEN), one of several ASD risk factors encoding negative regulators of the PI3K-Akt-mTOR pathway, have been reported in individuals with ASD and comorbid macrocephaly. We previously showed that a mouse model of Pten germline haploinsufficiency (Pten(+/-) ) has selective deficits, primarily in social behavior, along with broad overgrowth of the brain. Here, we further examine the social behavior of Pten(+/-) male mice in the resident-intruder test of aggression, using a comprehensive behavioral analysis to obtain an overall picture of the agonistic, non-agonistic and non-social behavior patterns of Pten(+/-) mice during a free interaction with a novel conspecific. Pten(+/-) male mice were involved in less aggression than their wild-type littermates. Pten(+/-) mice also performed less social investigation, including anogenital investigation and approaching and/or attending to the intruder, which is consistent with our previous finding of decreased sociability in the social approach test. In contrast to these decreases in social behaviors, Pten(+/-) mice showed increased digging. In summary, we report decreased aggression and increased repetitive behavior in Pten(+/-) mice, thus extending our characterization of this model of an ASD risk factor that features brain overgrowth and social deficits.