Comparison of DEG between neonatal male and female mice age of P25 by CHD8 Asn2373LysfsX2 heterozygote mutation.

CHD8, encoding a chromatin remodeling protein, is one of the most frequently mutated genes in autism spectrum disorders. However, how such mutations cause autistic behaviors remain unclear. In mice carrying a heterozygous frame-shift mutation in the Chd8 gene (Asn2373LysfsX2) identified in autistic human individuals, we observed autistic-like behaviors that are much stronger in males than in females, similar to human cases. These behaviors included enhanced mother-seeking ultrasonic vocalizations in pups, mother-attachment behaviors in juveniles, and isolation-induced self-grooming in adults. These behaviors were associated with opposite changes in synaptic excitation/inhibition and neuronal firing in male and female mice, but with strong changes in gene expression in female mice. Therefore, this CHD8 mutation may cause male-preponderant autistic-like behaviors in mice through differential synaptic/neuronal changes and gene expression Whole brain transcriptome of 3 neonatal WT and CHD8 Asn2373LysfsX2 heterozygote mutant mice age of P25 in both sex.CHD8编码染色质重塑蛋白，是自闭症谱系障碍（autism spectrum disorders）中最常见的突变基因之一。然而，此类突变引发自闭症行为的具体机制仍不明确。我们在携带自闭症患者中鉴定出的Chd8基因杂合移码突变（Asn2373LysfsX2）的小鼠模型中，观察到雄性小鼠的类自闭症行为显著强于雌性，这与人类病例的表现一致。此类行为包括幼鼠对母鼠的超声发声增强、幼年小鼠的母依恋行为，以及成年小鼠在隔离环境下诱导的自我梳理行为。这些行为与雌雄小鼠突触兴奋/抑制（synaptic excitation/inhibition）平衡及神经元放电的相反变化相关，但雌性小鼠的基因表达改变更为显著。综上，该CHD8突变可能通过差异性的突触/神经元改变及基因表达调控，在小鼠中引发雄性偏好的类自闭症行为。本数据集包含3只出生后第25天（P25）的雌雄两性野生型（wild type, WT）与CHD8 Asn2373LysfsX2杂合突变小鼠的全脑转录组数据。