Project Summary

Pascal S. Kaeser, M.D. (Young Investigator 2006) of the University of Texas Southwestern Medical Center at Dallas, plans to study in an animal model the role of the RIM1α gene in schizophrenia development. RlM1α is a presynaptic active zone protein that modulates synaptic plasticity. RlM1α knockout mice have extensive electrophysiological changes in short- and long-term synaptic plasticity and have a learning and memory deficit. Preliminary experiments suggest that RlM1α knockout mice exhibit schizophrenia-like behavioral traits. In the proposed project, Dr. Kaeser plans to create a RlM1α-serine-413-to-alanine knockin mouse line that lacks a critical phosphorylation site and a conditional RlM1α knockin/knockout mouse line to understand how modulatory synaptic defects result in schizophrenia-like symptoms. These lines will allow Dr. Kaeser to analyze the impact of a single phosphorylation site that regulates presynaptic forms of synaptic plasticity, and to create mice in which RIM1α la will be abolished in brain areas crucial for schizophrenia, such as the hippocampus. The mice also will be subject to behavioral experiments.

Program Area: SCHIZOPHRENIA/PSYCHOTIC DISORDERS\Schizophrenia

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