Age-differential sexual dimorphisms in CHD8-S62X-mutant mouse synapses and transcriptomes

Abstract

Chd8(+/N2373K) mice with a human C-terminal-truncating mutation (N2373K) display autistic-like behaviors in juvenile and adult males but not in females. In contrast, Chd8(+/S62X) mice with a human N-terminal-truncating mutation (S62X) display behavioral deficits in juvenile males (not females) and adult males and females, indicative of age-differential sexually dimorphic behaviors. Excitatory synaptic transmission is suppressed and enhanced in male and female Chd8(+/S62X) juveniles, respectively, but similarly enhanced in adult male and female mutants. ASD-like transcriptomic changes are stronger in newborn and juvenile (but not adult) Chd8(+/S62X) males but in newborn and adult (not juvenile) Chd8(+/S62X) females. These results point to age-differential sexual dimorphisms in Chd8(+/S62X) mice at synaptic and transcriptomic levels, in addition to the behavioral level.