Hypersociability in the Angelman syndrome mouse model

Exp Neurol. 2017 Jul;293:137-143. doi: 10.1016/j.expneurol.2017.04.002. Epub 2017 Apr 11.

Abstract

Deletions and reciprocal triplications of the human chromosomal 15q11-13 region cause two distinct neurodevelopmental disorders. Maternally-derived deletions or inactivating mutations of UBE3A, a 15q11-13 gene expressed exclusively from the maternal allele in neurons, cause Angelman syndrome, characterized by intellectual disability, motor deficits, seizures, and a characteristic increased social smiling, laughing, and eye contact. Conversely, maternally-derived triplications of 15q11-13 cause a behavioral disorder on the autism spectrum with clinical features that include decreased sociability that we recently reconstituted in mice with Ube3a alone. Based on the unique sociability features reported in Angelman syndrome and the repressed sociability observed when Ube3a gene dosage is increased, we hypothesized that mice with neuronal UBE3A loss that models Angelman syndrome would display evidence of hypersocial behavior. We report that mice with maternally-inherited Ube3a gene deletion (Ube3amKO) have a prolonged preference for, and interaction with, social stimuli in the three chamber social approach task. By contrast, interactions with a novel object are reduced. Further, ultrasonic vocalizations and physical contacts are increased in male and female Ube3amKO mice paired with an unfamiliar genotype-matched female. Single housing wild type mice increased these same social behavior parameters to levels observed in Ube3amKO mice where this effect was partially occluded. These results indicate sociability is repressed by social experience and the endogenous levels of UBE3A protein and suggest some social behavioral features observed in Angelman syndrome may reflect an increased social motivation.

Keywords: Angelman syndrome; Autism; Intellectual disability; Social behavior; UBE3A; Ultrasonic vocalizations.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Angelman Syndrome / complications*
  • Angelman Syndrome / genetics
  • Animals
  • Disease Models, Animal
  • Exploratory Behavior / physiology
  • Female
  • Male
  • Mice
  • Mice, Knockout
  • Motor Activity / genetics
  • Social Behavior Disorders / etiology*
  • Time Factors
  • Ubiquitin-Protein Ligases / deficiency*
  • Ubiquitin-Protein Ligases / genetics
  • Vocalization, Animal / physiology

Substances

  • Ube3a protein, mouse
  • Ubiquitin-Protein Ligases