Offspring genetic diversity regulates rearing experiences that predict differential susceptibility to Chd8 haploinsufficiency

Loss of function mutations in the autism-associated CHD8 gene are highly penetrant for trait and behavioral abnormalities in children, but there is substantial clinical heterogeneity in the occurrence and extent of disruptions between individuals. Using a large genetic reference panel of mice, we recently showed that this heterogeneity is, in part, regulated by genetic background. Here, we hypothesize that genetic background may also influence early life experiences, further shaping individual susceptibility to neurodevelopmental disorders. To test this, systematic observations were conducted to track behaviors during the rearing of genetically diverse Collaborative Cross offspring raised by genetically identical dams.