自闭症相关基因Neuroligin-4在小鼠海马区椎体神经元中的作用机制研究

Neuroligin-4（NL4）是定位于突触后膜的细胞粘附分子。NL4基因的突变与自闭症相关,但NL4突变的致病机理并不清楚。我们的合作者发现了一个与自闭症相关的新的NL4突变(NL4-R101Q）。我们的初步数据表明，在HEK293细胞中过表达NL4-R101Q使NL4蛋白变得不稳定，同时过表达NL4-R101Q降低NL4诱导突触形成的能力。本项目我们将通过制作两种新的NL4转基因小鼠并结合多种前沿研究技术，研究NL4如何影响突触的结构/功能以及NL4-R101Q如何影响小鼠的行为，本研究将有益于针对自闭症治疗手段的开发。

Neuroligin-4 (NL4) is a postsynaptic cell-adhesion molecule. Mutations in neuroligin-4 (NL4) have been repeatedly associated with autism spectrum disorders, however, the underlying mechanisms of NL4 mutations-mediated autism are still largely unknown. Our collaborator has recently found a single amino-acid substitution in NL4 (R101Q) that is associated with autism. Our preliminary data suggested that the NL4-R101Q substitution destabilized NL4 protein when overexpressed in HEK293 cell, and overexpression of NL4-R101Q decreased the ability to induce synapse by NL4. By creating two new mouse lines and using multiple cutting-edge technologies, our current project is trying to explore how NL4 affects synapse structure/function and how the NL4-R101Q affects mouse behaviors. Our current project will benefit the development of therapies against autism.