Autism and epilepsy have strong genetic components and significant comorbidity. Many mutations associated with both autism and epilepsy occur in the genes important for synapse formation, function and plasticity, suggesting overlapping molecular as well as circuit mechanisms. Understanding the defects of synapse development caused by these mutations will provide important insights to pathogenesis of both diseases and tools for therapeutic intervention. We found that components of planar cell polarity (PCP) pathway are localized in developing excitatory synapses and interact with multiple key presynaptic and postsynaptic proteins. Several point mutations in PRICKE1 and PRICKLE2 have been identified in patients with myoclonus epilepsy. Using CRISPR-Cas9-mediated gene editing, we generated mice that carry these human mutations. In this proposal, we will test whether these mice can serve as animal models to study how abnormal development can lead to these disorders.
Autism and epilepsy have strong genetic components and significant comorbidity. Using CRISPR-Cas9- mediated gene editing, we generated mice that carry human mutations to study how abnormal development can lead to these disorders.
