Our group has been characterizing the 16p11.2del mouse, a model of 16p11.2 Deletion Syndrome, one highly correlated with autism spectrum disorders. The 16p11.2 chromosomal region contains the ERK1 allele, coding for a protein critically important to cortical neurogenesis. In the 16p11.2+/- mouse, in addition to the anticipated 50% decrease in total ERK protein, there is a paradoxical increase in ERK phosphorylation. Downstream effects of this hyperactivation are an increase in density of deep layer neurons (Tbr1+) and a decrease in density in the upper layer neurons (Brn1+, Satb2+) in the somatosensory cortex. This model also displays behavioral abnormalities in novel object recognition, open field, elevated plus maze, and contextual fear conditioning. Currently, our lab is exploring a pharmacological rescue of this phenotype with ERK inhibitors.