GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE275nnn/GSE275742/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE275742GEOGSEfalseCortex, hippocampus, striatum transcriptome analysis of Chd8 mutation (Asn2373LysfsX2) adult mice with C57BL/6J x 129/Sv backgroundAutism spectrum disorders (ASD) are 4–5 times more common in males, possibly due to female protective effects (FPEs), which suggests females are less susceptible to ASD unless a genetic mutation is particularly strong. 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.2026/09/17GSE275742GSM8483817GSM8483738GSM8483815GSM8483739GSM8483816GSM8483813GSM8483736GSM8483737GSM8483814GSM8483778GSM8483734GSM8483811GSM8483735GSM8483779GSM8483812GSM8483787GSM8483743GSM8483744GSM8483788GSM8483741GSM8483785GSM8483742GSM8483786GSM8483783GSM8483784GSM8483740GSM8483781GSM8483782GSM8483780GSM8483749GSM8483747GSM8483748GSM8483745GSM8483789GSM8483746GSM8483754GSM8483798GSM8483799GSM8483755GSM8483796GSM8483752GSM8483797GSM8483753GSM8483750GSM8483794GSM8483751GSM8483795GSM8483792GSM8483793GSM8483790GSM8483791GSM8483758GSM8483759GSM8483756GSM8483757GSM8483765GSM8483766GSM8483763GSM8483764GSM8483761GSM8483762GSM8483760GSM8483808GSM8483809GSM8483729GSM8483806GSM8483807GSM8483804GSM8483805GSM8483728GSM8483802GSM8483769GSM8483803GSM8483767GSM8483800GSM8483801GSM8483768GSM8483776GSM8483732GSM8483810GSM8483733GSM8483777GSM8483730GSM8483774GSM8483775GSM8483731GSM8483772GSM8483773GSM8483770GSM848377121103275742Mus musculus[42106518]