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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21NS111648-01
Application #
9723902
Study Section
Synapses, Cytoskeleton and Trafficking Study Section (SYN)
Program Officer
Whittemore, Vicky R
Project Start
2019-04-15
Project End
2021-03-31
Budget Start
2019-04-15
Budget End
2021-03-31
Support Year
1
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of California, San Diego
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093