Leung Celeste, Jia Zhengping
The Hospital for Sick Children, Program in Neurosciences and Mental Health, Peter Gilgan Centre for Research and Learning, TorontoON, Canada; Program in Physiology, University of Toronto, TorontoON, Canada.
Front Genet. 2016 Mar 23;7:40. doi: 10.3389/fgene.2016.00040. eCollection 2016.
Over the past three decades, genetic manipulations in mice have been used in neuroscience as a major approach to investigate the in vivo function of genes and their alterations. In particular, gene targeting techniques using embryonic stem cells have revolutionized the field of mammalian genetics and have been at the forefront in the generation of numerous mouse models of human brain disorders. In this review, we will first examine childhood developmental disorders such as autism, intellectual disability, Fragile X syndrome, and Williams-Beuren syndrome. We will then explore psychiatric disorders such as schizophrenia and lastly, neurodegenerative disorders including Alzheimer's disease and Parkinson's disease. We will outline the creation of these mouse models that range from single gene deletions, subtle point mutations to multi-gene manipulations, and discuss the key behavioral phenotypes of these mice. Ultimately, the analysis of the models outlined in this review will enhance our understanding of the in vivo role and underlying mechanisms of disease-related genes in both normal brain function and brain disorders, and provide potential therapeutic targets and strategies to prevent and treat these diseases.
在过去三十年里，小鼠基因操作已成为神经科学研究基因体内功能及其改变的主要方法。特别是，利用胚胎干细胞的基因靶向技术彻底改变了哺乳动物遗传学领域，并在众多人类脑部疾病小鼠模型的构建中处于前沿地位。在本综述中，我们首先将研究儿童发育障碍，如自闭症、智力残疾、脆性X综合征和威廉姆斯-博伦综合征。然后，我们将探讨精神疾病，如精神分裂症，最后是神经退行性疾病，包括阿尔茨海默病和帕金森病。我们将概述这些小鼠模型的创建过程，从单基因缺失、细微点突变到多基因操作，并讨论这些小鼠的关键行为表型。最终，对本综述中概述的模型进行分析将增进我们对疾病相关基因在正常脑功能和脑部疾病中的体内作用及潜在机制的理解，并提供预防和治疗这些疾病的潜在治疗靶点和策略。
