Contactin-associated protein-like 2 (CASPR2, encoded by the gene CNTNAP2) is a cell adhesion molecule that is essential for proper neuronal function. Common and rare genetic variations in CNTNAP2 are associated with an increased risk of autism spectrum disorders. A recessive mutation in exon 22 of the gene causes a syndromic form of autism called cortical dysplasia-focal epilepsy syndrome (CDFE). CDFE is a common cause of intractable epilepsy in children, and the cerebral cortex of individuals with CDFE often shows a disorganized structure.
Elior Peles, in collaboration with Oscar Marin and Daniel Geschwind, is aiming to characterize two new CNTNAP2 mouse models. One model bears a mutation in exon 22, similar to the human mutation. In the second model, a marker gene replaces the first exon of CNTNAP2. The presence of the marker should allow the researchers to better understand the cellular changes that occur in mice with CNTNAP2 mutations. Peles’s lab has also generated model mice that lack CASPR2 completely.
The group plans to obtain detailed anatomical, developmental and behavioral data from mice with the exon 22 mutation, and then compare the data with those obtained from mice lacking CASPR2. This comparison could reveal underlying mechanisms relevant to autism. The researchers also plan to characterize the basic electrophysiological properties of microcircuits in the cerebral cortex of the model mice. Finally, they plan to examine the effects of several drugs that may modify social behavior in these newly generated model mice.