The goal of this work is to examine the role of the dopamine transporter (DAT) and the Mu Opioid Receptor (MOR) in age related disorders (DAT: Parkinsons Disease, neurotoxicity; MOR: pain, immune challenge). The strategy is via tissue specific, conditionally expressed transgenic mouse models. The ability to conditionally express a gene in a tissue specific manner is essential because only then can a resultant phenotype be assigned to a finite group of cells. This work is broken into three parts. The first two parts work with the DAT gene to characterize the genetic elements responsible for dopamine (DA) cell specific gene expression and, the spectrum of gene products (mRNAs) expressed in DA cells. With these tools, and the genes encoding DA cell-specific mRNAs, we hope to better choose future candidate genes to be conditionally expressed (or knocked out), and to further characterize the DNA sequences required to drive the expression of these genes uniquely to DA cells. The approach is to create a mouse harboring a loxp- inserted MOR gene, and in conjunction with tissue specific Cre expressing transgenic mice to create several different MOR knockout lines of mice, with each line knocking out the MOR in a different tissue. The first tissue targeted is the dorsal root ganglion to study the contributions of the MOR in peripheral analgesia.
