Autism spectrum disorder (ASD) is a neuronal developmental disorder with impaired social interaction and communication, often with abnormal intelligence and comorbidity with epilepsy. Disturbances in synaptic transmission, including the GABAergic, glutamatergic, and serotonergic systems, are known to be involved in the pathogenesis of this disorder, yet we do not know if there is a common molecular mechanism. As mutations in the GABAergic receptor subunit gene GABRA4 are reported in patients with ASD, we eliminated the Gabra4 gene in mice and found that the Gabra4 knockout mice showed autistic-like behavior, enhanced spatial memory, and attenuated susceptibility to pentylenetetrazol-induced seizures, a constellation of symptoms resembling human high-functioning autism. To search for potential molecular pathways involved in these phenotypes, we performed a hippocampal transcriptome profiling, constructed a hippocampal interactome network, and revealed an upregulation of the NMDAR system at the center of the converged pathways underlying high-functioning autism-like and anti-epilepsy phenotypes.

中文翻译：

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Gabra4基因敲除小鼠的转录组学揭示了自闭症，记忆和癫痫病的常见NMDAR通路。

自闭症谱系障碍（ASD）是一种神经元发育障碍，社交互动和沟通能力受损，通常伴有智力异常和合并性癫痫。已知这种疾病的发病机理涉及突触传递的障碍，包括GABA能，谷氨酸能和血清素能系统，但我们不知道是否存在共同的分子机制。由于在ASD患者中报告了GABA受体受体亚基基因GABRA4的突变，我们消除了小鼠中的Gabra4基因，发现Gabra4基因敲除小鼠表现出自闭症样行为，增强了空间记忆，并减弱了对戊四氮诱发的癫痫发作的敏感性。类似于人类高功能自闭症的症状。为了寻找涉及这些表型的潜在分子途径，