P2.89: Disorganized brain structure, epileptic seizures, and behavioral abnormalities in the CNTNAP2 knock out mouse

Autism is a neurodevelopmental disorder characterized by deficits in 3 core domains: social interaction, language development and repetitive behavior Association, 1994. Recently, a recessive mutation in the CNTNAP2 gene, which encodes for a transmembrane protein involved in neuron-glia interactions Poliak et al., 2003, has been associated to cortical dysplasia, focal epilepsy, hyperactivity and autism Strauss, 2006. To give further insight into the role of the CNTNAP2 gene in the development of autism we have characterized the behavioural and neuropathological phenotype of the knock out mouse for this gene. Mutant mice were obtained from Dr. Elior Peles Strauss, 2006 and were subsequently backcrossed for 10 generations to a B6/C57 background. Disruption of CNTNAP2 in mice mimics the neuropathology observed in the human mutation (Fig. 1). A, ectopic neurons in corpus callosum (NeuN). B, reactive astrocytes in dentate gyrus (GFAP). C (WT) and D (KO), disorganized disposition of late born cortical neurons (Cux1, layers II-IV). E (WT) and D (KO), disorganized Purkinje cell layer in cerebellum with ectopic Purkinje cells in the granular layer (Calbindin).