Absence of Preference for Social Novelty and Increased Grooming in Integrin β3 Knockout Mice: Initial Studies and Future Directions

Elevated whole blood serotonin 5-HT, or hyperserotonemia, is a common biomarker in autism spectrum disorder (ASD). The integrin beta 3 receptor subunit gene (ITGB3) is a quantitative trait locus for whole blood 5-HT levels. Recent work shows that integrin beta 3 interacts with the serotonin transporter (SERT) in both platelets and in the midbrain. Furthermore, multiple studies have now reported gene gene interaction between the integrin beta 3 and SERT genes in association with ASD. Given the lack of previous data on the impact of integrin beta 3 on brain or behavioral phenotypes, we sought to compare mice with decreased or absent expression of the integrin beta 3 receptor subunit (Itgb3+/- and -/-) with wildtype littermate controls in behavioral tasks relevant to ASD. These mice did not show deficits in activity level in the open field or anxiety-like behavior on the elevated plus maze, two potential confounds in the evaluation of mouse social behavior. In the three-chamber social test, mice lacking integrin beta 3 were shown to have normal sociability but did not show a preference for social novelty. Importantly, the absence of integrin beta 3 did not impair olfaction or the ability to recall familiar social odors. Additionally, mice lacking integrin beta 3 showed increased grooming behavior in novel environments. These preliminary studies reveal altered social and repetitive behavior in these mice, which suggests that the integrin beta 3 subunit may be involved in brain systems relevant to ASD. Further work is needed to fully characterize these behavioral changes and the underlying brain mechanisms.