Communication-related assessments in an Angelman syndrome mouse model

Peter A Perrino; Stormy J Chamberlain; Inge-Marie Eigsti; Roslyn Holly Fitch

doi:10.1002/brb3.1937

Communication-related assessments in an Angelman syndrome mouse model

Brain Behav. 2021 Jan;11(1):e01937. doi: 10.1002/brb3.1937. Epub 2020 Nov 5.

Authors

Peter A Perrino¹, Stormy J Chamberlain², Inge-Marie Eigsti³, Roslyn Holly Fitch¹

Affiliations

¹ Department of Psychological Science/Behavioral Neuroscience, University of Connecticut, Storrs, CT, USA.
² Department of Genetics and Genome Sciences, University of Connecticut Health Center, Farmington, CT, USA.
³ Department of Psychological Science/Clinical Psychology, University of Connecticut, Storrs, CT, USA.

Abstract

Introduction: Angelman syndrome (AS) is a neurodevelopmental disorder characterized by motor deficits, seizures, some autistic-like behaviors, and severe impairment of speech. A dysfunction of the maternally imprinted UBE3A gene, coupled with a functional yet silenced paternal copy, results in AS. Although studies of transgenic mouse models have revealed a great deal about neural populations and rescue timeframes for specific features of AS, these studies have largely failed to examine intermediate phenotypes that contribute to the profound communicative disabilities associated with AS.

Methods: Here, we use a variety of tasks, including assessments of rapid auditory processing and social communication. Expressive vocalizations were directly assessed and correlated against other core behavioral measures (motor, social, acoustic perception) to model putative influences on communication.

Results: AS mice displayed the characteristic phenotypes associated with Angelman syndrome (i.e., social and motor deficits), as well as marginal enhancements in rapid auditory processing ability. Our characterization of adult ultrasonic vocalizations further showed that AS mice produce fewer vocalizations and vocalized for a shorter amount of time when compared to controls. Additionally, a strong correlation between motor indices and ultrasonic vocalization output was shown, suggesting that the motor impairments in AS may contribute heavily to communication impairments.

Conclusion: In summary, the combination of motor deficits, social impairment, marginal rapid auditory enhancements, and altered ultrasonic vocalizations reported in a mouse model of AS clearly parallel the human symptoms of the disorder. This mouse model offers a novel route to interrogate the underlying genetic, physiologic, and behavioral influences on the under-studied topic of impaired communication in AS.

Keywords: UBE3A; angelman syndrome; auditory processing; motor system; neurodevelopment; ultrasonic vocalizations.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Angelman Syndrome* / genetics
Animals
Communication
Disease Models, Animal
Mice
Mice, Transgenic
Ubiquitin-Protein Ligases

Substances

Ubiquitin-Protein Ligases