Cellular and Molecular Neuroscience Laboratory, National Brain Research Centre, Manesar, Gurgaon 122 050, India.
Neural Plast. 2012;2012:710943. doi: 10.1155/2012/710943. Epub 2012 Jul 8.
Angelman syndrome (AS) is a neurodevelopmental disorder characterized by severe mental retardation, lack of speech, ataxia, susceptibility to seizures, and unique behavioral features such as easily provoked smiling and laughter and autistic features. The disease is primarily caused by deletion or loss-of-function mutations of the maternally inherited UBE3A gene located within chromosome 15q11-q13. The UBE3A gene encodes a 100 kDa protein that functions as ubiquitin ligase and transcriptional coactivator. Emerging evidence now indicates that UBE3A plays a very important role in synaptic function and in regulation of activity-dependent synaptic plasticity. A number of animal models for AS have been generated to understand the disease pathogenesis. The most widely used model is the UBE3A-maternal-deficient mouse that recapitulates most of the essential features of AS including cognitive and motor abnormalities. This paper mainly discusses various animal models of AS and how these models provide fundamental insight into understanding the disease biology for potential therapeutic intervention.
天使综合征（AS）是一种神经发育障碍，其特征为严重智力迟钝、语言缺失、共济失调、易发性癫痫发作以及独特的行为特征，如容易引发的微笑和笑声以及自闭症特征。该疾病主要由母系遗传的 UBE3A 基因（位于染色体 15q11-q13 内）缺失或功能丧失突变引起。UBE3A 基因编码一种 100 kDa 的蛋白质，其作为泛素连接酶和转录共激活因子发挥作用。现在有越来越多的证据表明 UBE3A 在突触功能和调节活性依赖性突触可塑性方面起着非常重要的作用。已经产生了许多 AS 的动物模型来了解疾病的发病机制。最广泛使用的模型是 UBE3A-母系缺陷小鼠，它重现了 AS 的大多数基本特征，包括认知和运动异常。本文主要讨论了 AS 的各种动物模型，以及这些模型如何为潜在的治疗干预提供理解疾病生物学的基本见解。
