Study on age-differential sexual dimorphism of mice carrying Chd8 S62X mutation

Abstract

Autism Spectrum Disorder (ASD) is around 4 times more common in males than in females. However, the mechanism underlying this sexual dimorphism remains poorly understood. In this study, we generated a new mouse line carrying a patient-mimicking S62X mutation in Chd8, an ASD risk gene. We found that adult male and female mice carrying Chd8 S62X mutation showed increase repetitive behavior and increased level of anxiety. However, at juvenile stage, only male showed increased anxiety-like attachment to mother. Transcriptomic analysis revealed that male mice showed alterations in transcriptome similar to that of the ASD patients at pup and juvenile stages, but not at adult stage. On the other hand, female mice showed transcriptomic pattern similar to ASD patients at pup and adult stages, but not at juvenile stage. Lastly, we found that excitatory synaptic transmission was also altered in an age-differential sexually dimorphic pattern. These results suggest mice carrying Chd8 S62X mutation as a new model to study sexual dimorphism of ASD.