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关于现有Neuroligin小鼠模型的总结

许均瑜, 夏强强, 夏军

浙江大学医学院神经生物学系，卫生部医学神经生物学重点实验室，浙江大学神经生物学重点实验，杭州 310058；香港科技大学生命科学部，香港

摘要

Neuroligin是位于神经元突触后膜并介导突触生成的一类细胞粘附分子。其家族蛋白可特异性介导兴奋性或抑制性突触形成。已有多项研究显示，Neuroligin基因突变与自闭症等精神发育迟滞疾病相关。而因neuroligin蛋白功能异常引起的系列变化亦在小鼠模型中得到印证。Neuroligin基因缺失，敲入或变异基因替代等小鼠模型，尤其是自闭症相关小鼠模型出现社交能力减弱，学习与记忆能力减退及强迫症相关表型，与人类自闭症症状相似。研究更进一步显示，该类小鼠中存在兴奋性突触及抑制性突触失调现象，并伴随有谷氨酸受体亚单位成分变化。然而，在小鼠模型研究中亦存在与体外研究结论不符情况，甚或出现相悖结论。在此综述中，我们总结了近几年所报道的小鼠模型，研究报道中的小鼠在分子，细胞及行为水平的各种异常现象，并归纳分析在各类小鼠中出现的相似及相异结果，希望能从中了解到neuroligin小鼠模型研究的进展及整体成果。

关键词： neuroligin; 突触生成; 突触功能; 自闭症; 小鼠模型

分类号：R394-3; R395.2

A review on the current neuroligin mouse models

XU Jun-Yu, Xia Qiang-Qiang, Xia Jun

Department of Neurobiology, Key Laboratory of Medical Neurobiology of Ministry of Health, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou 310058, China； Division of Life Science, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China

Abstract

Neuroligins (NLs) are postsynaptic membrane proteins expressed in the brain and mediate synaptogenesis. Neuroligin family proteins can specifically induce either excitatory or inhibitory synapses. Deletions or point mutations in neuroligin genes are found in patients with autism spectrum disorders (ASD) or mental retardations. The dysfunctions of these mutations have been tested in multiple neuroligin mouse models. In most of the models, including the human autism-linked NL3 and NL4 mutation mice, there are social interaction defects, memory impairment and repetitive behaviors. Researchers also found the excitatory/inhibitory synapse ratio altered in those mice, as well as receptor subunit composition. However, inconsistencies and debates also exist between different research approaches. In this review, we summarize the neuroligin mouse models currently available, examine the detailed alterations detected in those mice and compare the differences within different mouse models or different investigation methods, to obtain an overall picture of the current progress on neuroligin mouse models.

Key words: neuroligin; synaptogenesis; synapse function; autism; mice model

收稿日期：2012-08-10　　录用日期：2012-09-03

通讯作者：许均瑜　　E-mail: junyu@zju.edu.cn

引用本文：

许均瑜, 夏强强, 夏军. 关于现有Neuroligin小鼠模型的总结[J]. 生理学报 2012; 64 (5): 550-562.

XU Jun-Yu, Xia Qiang-Qiang, Xia Jun. A review on the current neuroligin mouse models. Acta Physiol Sin 2012; 64 (5): 550-562 (in Chinese with English abstract).