Male-Biased Social Deficits in Chd8+/R2219* Mouse Model of Autism Linked to Hippocampal Abnormalities

This preclinical study generated a CRISPR-Cas9 mouse model carrying a CHD8 mutation associated with autism risk and found that male mice exhibited greater social deficits mirroring human sex bias, alongside macrocephaly and whole-brain enlargement. MRI and functional connectivity analyses revealed that hippocampal expansion and disrupted hippocampal network connectivity specifically correlated with social deficit severity in males, establishing hippocampal pathology as a key neural substrate for sex-biased autism phenotypes.