BACKGROUND DLG2, also known as postsynaptic density protein-93 (PSD-93) or chapsyn-110, is an excitatory postsynaptic scaffolding protein that interacts with synaptic surface receptors and signaling molecules. A recent study has demonstrated that mutations in the DLG2 promoter region are significantly associated with autism spectrum disorder (ASD). Although DLG2 is well known as a schizophrenia-susceptibility gene, the mechanisms that link DLG2 gene disruption with ASD-like behaviors remain unclear. METHODS Mice lacking exon 14 of the Dlg2 gene (Dlg2-/- mice) were used to investigate whether Dlg2 deletion leads to ASD-like behavioral abnormalities. To this end, we performed a battery of behavioral tests assessing locomotion, anxiety, sociability, and repetitive behaviors. In situ hybridization was performed to determine expression levels of Dlg2 mRNA in different mouse brain regions during embryonic and postnatal brain development. We also measured excitatory and inhibitory synaptic currents to determine the impacts of Dlg2 deletion on synaptic transmission in the dorsolateral striatum. RESULTS Dlg2-/- mice showed hypoactivity in a novel environment. They also exhibited decreased social approach, but normal social novelty recognition, compared with wild-type animals. In addition, Dlg2-/- mice displayed strong self-grooming, both in home cages and novel environments. Dlg2 mRNA levels in the striatum were heightened until postnatal day 7 in mice, implying potential roles of DLG2 in the development of striatal connectivity. In addition, the frequency of excitatory, but not inhibitory, spontaneous postsynaptic currents in the Dlg2-/- dorsolateral striatum was significantly reduced. CONCLUSION These results suggest that homozygous Dlg2 deletion in mice leads to ASD-like behavioral phenotypes, including social deficits and increased repetitive behaviors, as well as reductions in excitatory synaptic input onto dorsolateral spiny projection neurons, implying that the dorsal striatum is one of the brain regions vulnerable to the developmental dysregulation of DLG2.

中文翻译：

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小鼠中的 DLG2 缺乏导致社交能力降低和重复行为增加，并伴有背侧纹状体中的异常突触传递。

背景 DLG2，也称为突触后密度蛋白93 (PSD-93) 或chapsyn-110，是一种与突触表面受体和信号分子相互作用的兴奋性突触后支架蛋白。最近的一项研究表明，DLG2 启动子区域的突变与自闭症谱系障碍 (ASD) 显着相关。尽管 DLG2 是众所周知的精神分裂症易感基因，但将 DLG2 基因破坏与 ASD 样行为联系起来的机制仍不清楚。方法 使用缺乏 Dlg2 基因外显子 14 的小鼠（Dlg2-/- 小鼠）来研究 Dlg2 缺失是否会导致 ASD 样行为异常。为此，我们进行了一系列行为测试，评估运动、焦虑、社交和重复行为。进行原位杂交以确定胚胎和出生后大脑发育过程中不同小鼠大脑区域中 Dlg2 mRNA 的表达水平。我们还测量了兴奋性和抑制性突触电流，以确定 Dlg2 缺失对背外侧纹状体突触传递的影响。结果 Dlg2-/- 小鼠在新环境中表现出低活性。与野生型动物相比，它们还表现出减少的社交方式，但正常的社交新奇识别。此外，Dlg2-/- 小鼠在家庭笼子和新环境中都表现出强烈的自我修饰能力。直到出生后第 7 天，小鼠纹状体中的 Dlg2 mRNA 水平升高，这意味着 DLG2 在纹状体连接发展中的潜在作用。此外，兴奋性而非抑制性的频率，Dlg2-/- 背外侧纹状体中的自发突触后电流显着降低。结易受 DLG2 发育失调影响的区域。