Mice Lacking or , or Both, Exhibit Behaviors Consistent with Neurodevelopmental Disorders.

, and Astrotactins () , are members of the Membrane Attack Complex/Perforin (MACPF) superfamily that are predominantly expressed in the mammalian brain during development. Genetic variation at the human and loci has been implicated in neurodevelopmental disorders. We, and others, have previously shown that mice exhibit behavior reminiscent of autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). We created mice and mice via the Cre-mediated LoxP system to investigate the effect of gene deletion on anatomy and behavior. Additionally, double knock-out mice were generated by interbreeding and mice. Genomic validation was carried out for each knock-out line, followed by histological, weight and behavioral examination. triple knock-out mice were also generated by crossing double knock-out mice with previously generated mice, and examined by weight and histological analysis. and mice differ in their behavior: mice are hyperactive, whereas mice exhibit marked changes in anxiety-response on the elevated plus maze. mice also show evidence of altered sociability. Both and mice have normal short-term memory, olfactory responses, pre-pulse inhibition, and motor learning. The double knock-out mice show behaviors of and mice, without evidence of new or exacerbated phenotypes. is important in moderation of anxiety, with potential relevance to anxiety disorders. dysfunction resulting in hyperactivity may be relevant to the association of ADHD with chromosome locus 1q25.2. and genes do not compensate in the mammalian brain and likely have distinct molecular or cell-type specific functions.