Comparison of DEG between neonatal male and female mice age of P0 by CHD8 Asn2373LysfsX2 heterozygote mutation

CHD8, encoding a chromatin remodeling protein, is one of the most frequently mutated genes in autism spectrum disorders (ASDs) 1-8. However, whether and how such mutations cause autistic behaviors remain unclear. Here we show that a human CHD8 mutation causes autistic-like behaviors and enhanced excitatory drive specifically in male mice. We found that knockin mice carrying a heterozygous frame-shift mutation in the Chd8 gene (Asn2373LysfsX2) identified in human individuals with ASDs (Chd8+/N2373K mice) display male-specific autistic-like behaviors. Gene transcript analysis shows that male and female Chd8+/N2373K neurons exhibit largely opposite changes in the levels of 29 mRNAs, nine of which correspond to known ASD-risk genes. These results suggest that a human CHD8 mutation causes male-specific autistic-like behaviors in mice in association with gender-specific differential changes in gene transcripts and excitatory drive in the brain. Overall design: Whole brain transcriptome of 3 neonatal WT and CHD8 Asn2373LysfsX2 heterozygote mutant mice in both sex.

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Jung H, Park H, Choi Y, Kang H, Lee E, Kweon H, Roh JD, Ellegood J, Choi W, Kang J, Rhim I, Choi SY, Bae M, Kim SG, Lee J, Chung C, Yoo T, Park H, Kim Y, Ha S, Um SM, Mo S, Kwon Y, Mah W, Bae YC, Kim H, Lerch JP, Paik SB, Kim E