Project Summary

Anthony Samuel LaMantia, Ph.D. (Independent Investigator 2004) of the University of North Carolina, Chapel Hill, proposes studying the developmental impact that certain candidate genetic regions and genes associated with schizophrenia have in mice. He plans to analyze the effect of removing one group of genes in mice, the analogues of which in humans are on chromosomal region 22q11and lead to velocardiofacial syndrome, a condition that increases the risk of a carrier of getting schizophrenia by 50 to 100 fold. He also plans on researching mice missing a single and double dose of the gene neuregulin (Nrg), a cell-to-cell signaling molecule which is most frequently mutated in schizophrenia patients. Many 22q11 genes are expressed in the developing forebrain, and Nrg is thought to modulate differentiation of glial cells and neuronal migration to appropriate locations in the developing cortex. Other evidence suggests the pathologic processes that lead to schizophrenia selectively compromise GABAergic inhibitory interneurons in the cerebral cortex. These developmental deficits might render cortical circuits vulnerable to further stress leading to pathogenesis and disease. In this proposal, Dr. LaMantia will test in genetically engineered mice whether the 22q11 genes and Nrg influence the migration and differentiation of GABAergic inhibitory interneurons. These observations will better define the GABAergic interneuron as a pathological as well as therapeutic target in schizophrenia and better characterize the role of the 22q11 genes and Nrg in schizophrenia.

Program Area: SCHIZOPHRENIA/PSYCHOTIC DISORDERS\Schizophrenia

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