Effects of prenatal stress and/or forebrain ATRX deficiency in C57Bl/6 mice on regulation and expression of Autism risk genes

Abstract

Early life experiences influence brain development and consequently, behaviour into adulthood. In humans, maternal stress during the third trimester has been associated with increased incidences of Autism Spectrum Disorder (ASD). In human idiopathic ASD, expression of several genes is dysregulated, including Atrx, which encodes a chromatin remodeler responsible for widespread regulation of gene expression. Atrx expression is influenced by early life experiences. In this study, we investigated the effect of reduced ATRX, through genetic manipulation or by early prenatal stress exposure, on expression and promoter regulation of ASD risk genes. We found that mice exposed to stress in utero and that received low quality maternal care, had reduced ATRX and mTOR in the adult brain, and reduced methylation at both the Atrx and Mtor promoters, suggesting that early life experiences are capable of regulating ASD risk genes. This study expands our understanding of epigenetic mechanisms involved in programming ASD-like phenotypes.