Altered neuroligin expression is involved in social deficits in a mouse model of the fragile X syndrome
Altered neuroligin expression is involved in social deficits in a mouse model of the fragile X syndrome
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DOI：
10.1016/j.bbr.2009.11.019
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发表时间：
2010-03-17
影响因子：
2.7
通讯作者：
El-Husseini, Alaa
中科院分区：
文献类型：
--
作者：
Dahlhaus, Regina;El-Husseini, Alaa
脆性X综合征（FXS）是遗传性智力低下的最常见形式。脆性X智力低下蛋白（FMRP）是一种mRNA结合蛋白，其转录沉默导致翻译失调，被认为是脆性X综合征的主要原因。有趣的是，最近的研究结果表明，几个神经连接素相互作用的蛋白受到这种失调，包括neurexin 1和PSD 95，这也被牵连在autism spectrum disorders.Using免疫共沉淀分析和RT-PCR，FMRP显示与神经连接素1和2-mRNA相互作用，而没有观察到与神经连接素3-mRNA的相互作用。与FMRP在翻译调节中的作用一致，蛋白质印迹和免疫组织化学分析揭示了蛋白质表达水平的变化，表明突触功能受损。随着越来越多的证据表明神经连接素的表达是至关重要的突触成熟和功能，受损的神经连接素I的表达在FXS的后果进行了评估过表达HA-神经连接素1 FMR 1-/-小鼠，模型FXS。行为评估表明，增强神经连接素1的表达改善FMR 1-/-小鼠的社会行为，而没有看到积极的影响学习和记忆。这些结果提供了第一次证据的神经连接素neurexin蛋白网络参与FXS的核心症状。(C)2009 Elsevier B. V.保留所有权利。
The fragile X syndrome (FXS) is the most common form of inherited mental retardation. Caused by a transcriptional silencing of the fragile X mental retardation protein (FMRP),a mRNA binding protein itself, misregulated translation is thought to be the leading cause of the fragile X syndrome. Interestingly, recent results indicated several neuroligin interacting proteins to be affected by this misregulation, including neurexin1 and PSD95, which have also been implicated in autism spectrum disorders.Using co-immunoprecipitation assays and RT-PCR, FMRP is shown to interact with neuroligin1 and 2-mRNA, while no interaction with neuroligin3-mRNA is observed. In line with FMRP's role in translation regulation, Western blot as well as immunohistochemistry analysis reveal changes in protein expression levels suggesting impaired synaptic function. As increasing evidence indicates neuroligin expression to be critical for synapse maturation and function, consequences of impaired neuroligin I expression in FXS are assessed by overexpressing HA-neuroligin1 in FMR1-/- mice, a model for FXS.Behavioural assessments demonstrate that enhanced neuroligin1 expression improves social behaviour in FMR1-/- mice, whereas no positive effect on learning and memory is seen. These results provide for the first time evidence for an involvement of a neuroligin-neurexin protein network in core symptoms of FXS. (C) 2009 Elsevier B.V. All rights reserved.