Project Summary

Amelia Gallitano-Mendel, M.D., Ph.D. (Young Investigator 2006) of Washington University, will use an animal model to study the gene Egr3’s role in schizophrenia. As a molecular link between environmental events and the regulation of brain gene expression, the gene Egr3 may explain how both genetic and environmental factors contribute to the risk of developing schizophrenia. Egr3 maps to a major schizophrenia locus and is regulated in two protein pathways implicated in schizophrenia pathogenesis. Also, Dr. Gallitano-Mendel has found Egr3-deficient mice display schizophrenia-like abnormalities. Further, clozapine reverses hyperactivity and reduces aggressive behavior in the Egr3-deficient mice. Egr3-deficient mice also demonstrate resistance to clozapine’s sedating effects, seen in schizophrenia patients but not controls. Dr. Gallitano-Mendel proposes to use this effect to investigate how clozapine works and to identify the schizophrenic-like abnormalities in Egr3-deficient mice. The Egr-3-deficient mouse may also allow study of early treatment with antipsychotics as possible preventives for schizophrenia-like behavior during adulthood. Findings may lead to new targets for schizophrenia medications.

Program Area: SCHIZOPHRENIA/PSYCHOTIC DISORDERS\Schizophrenia

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