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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。
Neuroligin is a type of cell adhesion molecule located in the postsynaptic membrane of neurons and mediating synaptogenesis. Its family of proteins specifically mediate excitatory or inhibitory synapse formation. A number of studies have shown that neuroligin mutations are associated with mental retardation disorders such as autism. A series of changes caused by the abnormal function of neuroligin protein have also been confirmed in the mouse model. Neuroligin gene deletion, knock-in or mutation gene replacement and other mouse models, especially in autistic mouse models associated with weakened social skills, decreased learning and memory and obsessive-compulsive disorder phenotype, similar to the symptoms of human autism. The study further shows that excitatory synapses and inhibitory synapse dysregulation exist in these mice, accompanied by changes in the glutamate receptor subunit composition. However, there are some inconsistencies between the results of in vitro studies and the contradictory results in the study of mouse models. In this review, we summarize the mouse models reported in recent years to study the various abnormalities at the molecular, cellular and behavioral levels of the reported mice and to analyze the similarities and differences between the various mouse types Different results, hoping to understand the progress of neuroligin mouse model and the overall results.