Heterogeneity of p53 dependent genomic responses following ethanol exposure in a developmental mouse model of fetal alcohol spectrum disorder

This study examined if p53 was essential in the brain’s response to alcohol using a mouse model of fetal alcohol spectrum disorder (FASD) that involved the equivalent of a single day of binge drinking. We quantified the amount of cell death in specific brain regions and examined the levels of gene expression in these regions 8 hours after alcohol exposure using RNA-seq. Contrary to expectations, we found that cell death still occurred at the same or greater level in the brains of mice lacking p53 as in normal mice. However, we also found evidence that the lack of p53 greatly affected the expression of groups of genes involved in brain cell communication and metabolism. Somatosensory cortex was removed from wildtype (WT) and p53 knockout (KO) male mice on postnatal day 7, 8 hours after an IP injection of ethanol. Brains were flash frozen on dry ice, and RNA was harvested using Trizol reagent followed by RNeasy (Qiagen). Illumina Stranded RNA libraries were prepared using the RS-122-2101 Sample Prep Kit with 200-300 nanograms of total RNA for the starting material.