Tissue Specific Expression of DAT & MOR Transgenes in the Study of Aging Diso

这项工作的目标是研究 多巴胺转运体(DAT)与Mu阿片受体(MOR) 在年龄相关障碍(DAT：帕金森氏病，神经毒性； MOR：疼痛，免疫挑战)。这种策略是通过组织特异性的， 有条件表达的转基因小鼠模型。有能力 以特定于组织的方式有条件地表达基因是必不可少的 因为只有这样，才能将结果表型分配给有限的 一组单元格。这部作品分为三个部分。前两个 部分与DAT基因一起工作，以表征遗传要素 负责多巴胺(DA)细胞特异性基因的表达， DA细胞表达的基因产物(MRNAs)谱。 有了这些工具，以及编码DA细胞特异性mRNAs的基因， 我们希望更好地选择未来的候选基因来有条件地 表达(或敲除)，并进一步表征DNA 唯一驱动这些基因表达所需的序列 到DA细胞。方法是创造一只藏有loxP的老鼠- 插入MOR基因，并与组织特异性Cre结合 表达转基因小鼠以建立几种不同的模型 敲除老鼠的线条，每一条线条都敲除了MOR 不同的组织。第一个目标组织是背根神经节 目的：研究吗啡在外周镇痛中的作用。

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.