Angelman syndrome (AS) is a rare genetic disorder characterized by severe intellectual disability, seizures, lack of speech, and ataxia. The gene responsible for AS was identified as Ube3a and it encodes for E6AP, an E3 ubiquitin ligase. Currently, there is very little known about E6AP's mechanism of action in vivo or how the lack of this protein in neurons may contribute to the AS phenotype. Elucidating the mechanistic action of E6AP would enhance our understanding of AS and drive current research into new avenues that could lead to novel therapeutic approaches that target E6AP's various functions. To facilitate the study of AS, we have generated a novel rat model in which we deleted the rat Ube3a gene using CRISPR. The AS rat phenotypically mirrors human AS with loss of Ube3a expression in the brain and deficits in motor coordination as well as learning and memory. This model offers a new avenue for the study of AS. Autism Res 2020, 13: 397–409. © 2020 International Society for Autism Research,Wiley Periodicals, Inc.

中文翻译：

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具有完整的Ube3a基因缺失的Angelman综合征新型大鼠模型的产生。

Angelman综合征（AS）是一种罕见的遗传性疾病，其特征是严重的智力残疾，癫痫发作，言语不足和共济失调。负责AS的基因被鉴定为Ube3a，它编码E3AP泛素连接酶E6AP。目前，关于E6AP的体内作用机制或神经元中这种蛋白质的缺乏如何可能导致AS表型的了解甚少。阐明E6AP的机械作用将增强我们对AS的理解，并推动当前对新途径的研究，这些新途径可能会导致针对E6AP各种功能的新型治疗方法。为了促进AS的研究，我们生成了一种新的大鼠模型，其中删除了大鼠Ube3a基因使用CRISPR。AS大鼠在表型上反映了人类AS，其大脑中Ube3a表达的丧失和运动协调以及学习和记忆的缺陷。该模型为AS的研究提供了新的途径。Autism Res 2020，13：397–409。©2020国际自闭症研究协会，Wiley Periodicals，Inc.。