P2.90: Knockdown of CNTNAP2A causes morphological and behavioural changes in zebrafish

CNTNAP2 encodes the protein contactin associated protein like 2, a neurexin IV family cell adhesion molecule. Mutations in CNTNAP2 have been associated with cortical dysplasia – focal epilepsy, autism spectrum disorders, and specific language impairment. To study the functional role of CNTNAP2 in the nervous system, we utilized a Zebrafish morpholino-knockdown approach. We demonstrate that knockdown of Cntnap2a causes a smaller head phenotype. Furthermore, we observe a longer duration and altered tail movement during an evoked escape response assay. Assessment of the spinal cord shows a quantitative loss of GAD + cells within the spinal cord suggesting a possible explanation for the altered behaviour. We conclude that reduction of Cntnap2a causes a loss of gabaergic neurons, by a yet unknown mechanism, leading to gross morphologic and behavioural changes. These data supports the excitatory-inhibitory imbalance hypotheses that have been previously proposed for epilepsy and Autism Spectrum Disorders and suggests a possible new function for CNTNAP2 within the nervous system.