Excessive laughter-like vocalizations, microcephaly, and translational outcomes in the ube3a deletion rat model of angelman syndrome

Elizabeth L. Berg, Shekib A. Jami, Stela P. Petkova, Annuska Berz, Timothy A. Fenton, Jason P. Lerch, David J. Segal, John A. Gray, Jacob Ellegood, Markus Wöhr, Jill L. Silverman

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Angelman syndrome (AS) is a rare genetic neurodevelopmental disorder characterized by intellectual disabilities, motor and balance deficits, impaired communication, and a happy, excitable demeanor with frequent laughter. We sought to elucidate a preclinical outcome measure in male and female rats that addressed communication abnormalities of AS and other neurodevelopmental disorders in which communication is atypical and/or lack of speech is a core feature. We discovered, and herein report for the first time, excessive laughter-like 50 kHz ultrasonic emissions in the Ube3amat-/pat1 rat model of AS, which suggests an excitable, playful demeanor and elevated positive affect, similar to the demeanor of individuals with AS. Also in line with the AS phenotype, Ube3amat-/pat1 rats demonstrated aberrant social interactions with a novel partner, distinctive gait abnormalities, impaired cognition, an underlying LTP deficit, and profound reductions in brain volume. These unique, robust phenotypes provide advantages compared with currently available mouse models and will be highly valuable as outcome measures in the evaluation of therapies for AS.

Original languageEnglish (US)
Pages (from-to)8801
Number of pages1
JournalJournal of Neuroscience
Volume41
Issue number42
DOIs
StatePublished - Oct 20 2021
Externally publishedYes

Keywords

  • Angelman syndrome
  • Behavior
  • Play
  • Rat
  • Ube3a
  • Ultrasonic vocalization

ASJC Scopus subject areas

  • Neuroscience(all)

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