This is a request for an NIMH RSDA level 11 award that will allow me to keep my focus on research, and to develop new skills that will improve my ability to apply molecular biology to the nervous system. The present proposal is part of an effort to complete a detailed analysis of the molecular mechanisms regulating expression of the proenkephalin gene. Understanding the mechanisms which determine neural phenotypes during, development and which permit subsequent plasticity are among the central goals of neuroscience. At a fundamental level, both of these processes depend upon differential control of gene expression. I have been investigating the molecular mechanisms regulating expression of neurotransmitter genes, focusing on the gene encoding the opioid peptide precursor, proenkephalin. This ene is an ideal model because it is well studied, physiologically important, has an interesting pattern of cell-type specific expression, and is highly regulated by neurotransmitters, electrical stimulation, seizures, arid psychotropic drugs. This grant application requests support to continue on going studies of the mechanisms by which proenkephalin gene expression is regulated at the level of cis-regulatory elements and transacting factors, but shifting the emphasis to the regulation of cell type specific expression. It is proposed to apply these studies to the nervous system by producing transgenic mice. Because the production and detailed histologic analysis of transgenic mice are new techniques to me, this proposal will contribute significantly to my career development.
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