Department of Molecular Pharmacology and Physiology, University of South Florida, Tampa, Florida.
PTC Therapeutics Inc., Plainfield, 07080, New Jersey.
Autism Res. 2020 Mar;13(3):397-409. doi: 10.1002/aur.2267. Epub 2020 Jan 21.
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. LAY SUMMARY: Angelman syndrome (AS) is a rare genetic disorder characterized by severe intellectual disability, seizures, difficulty speaking, and ataxia. The gene responsible for AS was identified as UBE3A, yet very little is known about its function in vivo or how the lack of this protein in neurons may contribute to the AS phenotype. 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 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.
天使综合征（AS）是一种罕见的遗传性疾病，其特征是严重的智力障碍、癫痫发作、言语障碍和共济失调。导致 AS 的基因已被确定为 UBE3A，它编码 E6AP，一种 E3 泛素连接酶。目前，人们对 E6AP 在体内的作用机制或这种蛋白在神经元中的缺失如何导致 AS 表型知之甚少。阐明 E6AP 的作用机制将增强我们对 AS 的理解，并推动当前的研究进入新的途径，这些途径可能导致针对 E6AP 各种功能的新治疗方法。为了促进 AS 的研究，我们使用 CRISPR 技术在大鼠中删除了大鼠 Ube3a 基因，从而产生了一种新的大鼠模型。AS 大鼠表型与人类 AS 相似，大脑中 Ube3a 表达缺失，运动协调以及学习和记忆能力受损。这种模型为 AS 的研究提供了一个新途径。自闭症研究 2020, 13: 397-409. © 2020 国际自闭症研究协会，Wiley Periodicals, Inc. 概述：天使综合征（AS）是一种罕见的遗传性疾病，其特征是严重的智力障碍、癫痫发作、言语障碍和共济失调。导致 AS 的基因已被确定为 UBE3A，然而，人们对其在体内的功能或这种蛋白在神经元中的缺失如何导致 AS 表型知之甚少。为了促进 AS 的研究，我们使用 CRISPR 技术在大鼠中删除了大鼠 Ube3a 基因，从而产生了一种新的大鼠模型。AS 大鼠与人类 AS 相似，大脑中 Ube3a 表达缺失，运动协调以及学习和记忆能力受损。这种模型为 AS 的研究提供了一个新途径。
