As such, En2<sup>-/-</sup> mice display the behavioral deficits and neural impairments characteristic of the core symptoms associated with autism spectrum disorder (ASD).
Accordingly, mice lacking the En2 homeodomain (En2<sup>hd/hd</sup>, referred to as En2<sup>-/-</sup>) show molecular, anatomical and behavioral "ASD-like" features.
Elevated 5-hydroxymethylcytosine in the Engrailed-2 (EN-2) promoter is associated with increased gene expression and decreased MeCP2 binding in autism cerebellum.
Further support that EN2 is a possible ASD susceptibility gene requires the identification of a risk allele, a DNA variant that is consistently associated with ASD but is also functional.
Together, these data provide further genetic evidence that EN2 might act as an ASD susceptibility locus, and they suggest that a risk allele that perturbs the spatial/temporal expression of EN2 could significantly alter normal brain development.