• Neuroscience · Nov 2019

    Behavioral Evaluation of Angelman Syndrome Mice at Older Ages.

    • Rebecca Dutta and Jacqueline N Crawley.
    • MIND Institute, Department of Psychiatry and Behavioral Sciences, University of California Davis School of Medicine, Sacramento, CA 95817, USA.
    • Neuroscience. 2019 Nov 12.

    AbstractAngelman syndrome is a neurodevelopmental disorder presenting with severe deficits in motor, speech, and cognitive abilities. The primary genetic cause of Angelman syndrome is a maternally transmitted mutation in the Ube3a gene, which has been successfully modeled in Ube3a mutant mice. Phenotypes have been extensively reported in young adult Ube3a mice. Because symptoms continue throughout life in Angelman syndrome, we tested multiple behavioral phenotypes of male Ube3a mice and WT littermate controls at older adult ages. Social behaviors on both the 3-chambered social approach and male-female social interaction tests showed impairments in Ube3a at 12 months of age. Anxiety-related scores on both the elevated plus-maze and the light ↔ dark transitions assays indicated anxiety-like phenotypes in 12 month old Ube3a mice. Open field locomotion parameters were consistently lower at 12 months. Reduced general exploratory locomotion at this age prevented the interpretation of an anxiety-like phenotype, and likely impacted social tasks. Robust phenotypes in middle-aged Ube3a mice appear to result from continued motor decline. Motor deficits may provide the best outcome measures for preclinical testing of pharmacological targets, towards reductions of symptoms in adults with Angelman syndrome.Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.

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