Exploring the Dynamics of Social Interactions During the Juvenile Stage in a Mouse Model of Fragile X Syndrome

Abstract

AbstractIntroductionFragile X Syndrome (FXS), caused by mutations in theFmr1gene, is a neurodevelopmental condition linked to cognitive and behavioral differences, including atypical interactions and heightened anxiety-like responses in social settings. Previous studies that used FXS mouse models focused mostly on adulthood but not on behaviors displayed by juvenile mice. This is especially concerning considering the extensive body of research conducted in children and adolescents with FXS, which indicates dynamic neurodevelopmental changes from childhood to adulthood. Thus, it is crucial to study how FXS affects social interactions during the juvenile stage, in both female and male mice. In this study, we compared the social behavior ofFmr1knockout (KO) mice, a model of FXS, with wild-type (WT) mice of the C57BL/6J strain.MethodsWe examined both male and female juvenile mice at postnatal day 40 (P40). Social interaction tests were carried out using two mice of the same sex and genotype, who previously had not encountered each other, and were allowed to interact freely in an empty chamber for 10 minutes. Their behaviors were recorded by an overhead camera for 10 minutes. Key social behaviors such as head, body, anogenital sniffing, and physical touch, as well as distance traveled, were analyzed with a recently developed marker-less tracking software.ResultsResults from the social interaction tests showed pronounced sex and genotype differences between juvenile females and males of both the WT and KO genotypes. Overall, sex differences were found in all the behavioral parameters that were measured. Notably, the KO females engaged in more social interaction events compared to WT females in each social behavior. On the other hand, there were no significant differences observed between the WT and KO males.DiscussionThese results highlight the importance of considering the differences that arise during the juvenile stage inFmr1KO mouse model, suggesting that early post-natal phases may be a promising window for therapeutic interventions.