Generation of a Novel Rat Model of Angelman Syndrome with a Complete Ube3a Gene Deletion.
Generation of a Novel Rat Model of Angelman Syndrome with a Complete Ube3a Gene Deletion.
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DOI：
10.1002/aur.2267
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发表时间：
2020-03
期刊：
影响因子：
--
通讯作者：
Nash KR
中科院分区：
文献类型：
--
作者：
Dodge A;Peters MM;Greene HE;Dietrick C;Botelho R;Chung D;Willman J;Nenninger AW;Ciarlone S;Kamath SG;Houdek P;Sumová A;Anderson AE;Dindot SV;Berg EL;O'Geen H;Segal DJ;Silverman JL;Weeber EJ;Nash KR
安格曼综合征（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、失语和共济失调。负责 AS 的基因被鉴定为 Ube3a，它编码 E6AP（一种 E3 泛素连接酶）。目前，人们对 E6AP 的体内作用机制或神经元中缺乏这种蛋白如何导致 AS 表型知之甚少。阐明 E6AP 的机制作用将增强我们对 AS 的理解，并推动当前研究进入新途径，从而可能产生针对 E6AP 各种功能的新治疗方法。为了促进 AS 的研究，我们构建了一种新型大鼠模型，其中我们使用 CRISPR 删除了大鼠 Ube3a 基因。 AS 大鼠的表型与人类 AS 相似，大脑中 Ube3a 表达缺失，运动协调以及学习和记忆能力缺陷。该模型为AS的研究提供了新的途径。安格曼综合征 (AS) 是一种罕见的遗传性疾病，其特征是严重智力障碍、癫痫、说话困难和共济失调。负责 AS 的基因被鉴定为 UBE3A，但对其体内功能或神经元中缺乏这种蛋白质如何导致 AS 表型知之甚少。为了促进 AS 的研究，我们构建了一种新型大鼠模型，其中我们使用 CRISPR 删除了大鼠 Ube3a 基因。 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缺陷。该模型为AS的研究提供了新的途径。
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. 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.
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影响因子：
2.7
作者：
Arrant, Andrew E.;Schramm-Sapyta, Nicole L.;Kuhn, Cynthia M.
通讯作者：
Kuhn, Cynthia M.
影响因子：
0.2
作者：
Parasuraman S
通讯作者：
Parasuraman S
影响因子：
2.9
作者：
Allensworth, Melody;Saha, Anand;Heck, Detlef H.
通讯作者：
Heck, Detlef H.
DOI：
10.1111/jar.12462
发表时间：
2018-11-01
影响因子：
2.4
作者：
Grieco, Joseph C.;Gouelle, Arnaud;Weeber, Edwin J.
通讯作者：
Weeber, Edwin J.
影响因子：
3
作者：
PELLOW, S;CHOPIN, P;BRILEY, M
通讯作者：
BRILEY, M