Hippocampus transcriptome analysis of CHD8 Asn2373LysfsX2 heterozygote mutation mice age of P25. Mus musculus

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 Overall design: Hippocampus transcriptome of WT and CHD8 Asn2373LysfsX2 heterozygote mutant mice age of P25 in both sex.