Mechanisms regulating proenkephalin gene expression: contributions of transgenic models

This chapter gives an overview of the utility of one type of transgenic mouse model for substance abuse research, the use of transgenes in which genomic regulatory sequences of interest are coupled to a reporter gene. Using this mouse model, exploration of the mechanisms regulating expression of the proenkephalin gene in the mouse hypothalamus have begun. The resulting information supplements experiments on gene regulation performed in cell lines with information about regulation by pharmacologic and physiologic stimuli of interest within the brain. With special reference to mechanisms of opioid dependence, the particular model that has been examined appears to be a useful tool to investigate mechanistic aspects of the regulation of endogenous opioid genes by exogenous opioids.