| Epilepsy is a devastating disease that affects 1% of the world’s population, yet for 70% of patients the cause remains unknown, leading to inadequate clinical treatment and poor prognosis. Often times, epilepsy is a result of abnormal neuronal development that leads to a hyper excitable neuronal network. The Wnt signaling pathway plays a key role in neuronal development and excitability, and mutations of genes in this pathway lead to epilepsy. PRICKLE1 is a member of a protein family(including the closely related PRICKLE2), which share a highly conserved PET/LIM domain. Prickle1 and Prickle2 participate in the non-canonical planar cell polarity (PCP) Wnt signaling pathway. We recently identified several patients from families with mutations in Prickle proteins that have epilepsy with and without ataxia. However, we do not fully understand the molecular mechanisms by which these mutations contribute to the etiology of epilepsy and overall neurological dysfunction. To investigate this question, our laboratory generated several mouse lines with null and point mutant alleles for Prickle1 and Prickle2. |