Aberrant aggressive behavior in a mouse model of Angelman syndrome

Abstract

Angelman syndrome (AS) is a genetic neurodevelopmental disorder due to the absence of the E3-ligase protein, UBE3A. Inappropriate social interactions, usually hyper-sociability, is a part of that syndrome. In addition, clinical surveys and case reports describe aggressive behavior in AS individuals as a severe difficulty for caretakers. A mouse model for AS recapitulates most of the human AS phenotypes. However, very few studies utilized this mouse model for investigating affiliative social behavior, and not even a single study examined aggressive behavior. Hence, the aim of the herein study was to examine affiliative and aggressive social behavior. For that, we utilized a battery of behavioral paradigms, and performed detailed analyses of these behaviors. AS mice exhibited a unique characteristic of reduced habituation towards a social stimulus in comparison to their wild-type (WT) littermates. However, overall there were no additional marked differences in affiliative social behavior. In contrast to the mild changes in affiliative behavior, there was a striking enhanced aggression in the AS mice compared to their WT littermates. The herein findings emphasize the use of AS mouse model in characterizing and measuring inappropriate aggressive behavior, and suggests these as tools for investigating therapeutic interventions aimed at attenuating aggressive behavior.

Adolescent parvalbumin expression in the left orbitofrontal cortex shapes sociability in female mice

“…Our data suggest that socially evoked activity in the OFC L is important for reducing social approaching behaviors when the animal becomes an adult. Excessive sociability is a symptom of patients with Williams-Beuren syndrome (Mimura et al, 2010; Sakurai et al, 2011; Segura-Puimedon et al, 2014; Stoppel and Anderson, 2017) or Angelman syndrome (Stoppel and Anderson, 2017; Simchi and Kaphzan, 2021), rare neurodevelopmental genetic disorders. Interestingly, these patients show abnormal activity patterns in the OFC.…”