Angelman syndrome (AS) is a neurodevelopmental disorder characterized by cognitive impairment, absent speech, seizures, motor and sleep impairments, and caused by loss of function of the maternal copy of the UBE3A gene. Modeling the AS phenotype in preclinical models across behavioral domains is critical for testing of new therapeutics. Our previous work reported behavioral phenotypes in male Ube3am-/p+ (AS model) mice on a cognitive-like operant extinction task.
Here, we evaluated operant task performance in male and female Ube3am-/p+ mice across two cohorts, and correlated operant performance with performance on a battery of other widely used behavioral tests for Ube3a mutants. Ube3am-/p+ mice showed impairments in both the acquisition and extinction phases of operant testing that were not sex-specific. Inclusion of operant testing in the existing Ube3am-/p+ behavioral battery was feasible and improved clustering of genotypes in principal component space.
Overall, operant acquisition and extinction testing is a reliable approach to quantify cognitive-like learning impairments in Ube3am-/p+ mice. Operant testing should be considered as part of a broad toolbox for evaluating the effectiveness of AS treatments preclinically. Work was supported by NIH R00EY028964 to MSS, NIH T32NS115656 to CDG, a grant from the Angelman Syndrome Foundation to MSS, and the District of Columbia Intellectual and Developmental Disabilities Research Center (DC-IDDRC) Award P50HD105328 by NICHD.
Li Wang (Children’s National) for assistance with open field testing. Kerr have contributed equally. Center for Neuroscience Research, Children’s National Hospital, Washington, DC, USA Caleigh D.
Sidorov Departments of Pediatrics and Pharmacology & Physiology, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA The authors declare no competing interests. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material.
You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
Extract — continue reading at the source.
