Whole brain transcriptome analysis of heterozygous and homozygous Chd8 mutation (Asn2373LysfsX2) mice age of P0, P25 and P56 with C57BL6/J x 129/Sv background

If this is the case, increasing the strength of a ASD-risk mutation above the female threshold may induce ASD symptoms both in females and males. To this end, we compared male and female phenotypes in heterozygous and homozygous mice carrying a patient-derived CHD8 mutation (Asn2373LysfsX2), using a hybrid genetic background to overcome homozygous lethality.

Heterozygous Chd8+/N2373K males and females displayed sexually dimorphic phenotypes stronger than those in homozygous Chd8 N2373 /N2373K males and females in behaviors, brain blood flow, neuronal activity, synaptic transmission, and transcriptomes. These results suggest that a stronger Chd8 mutation suppresses sexual dimorphism in mice, supporting the FPE hypothesis in ASD.