The recent development of methods for engineering bacterial artificial chromosomes (BACs), and for the efficient production of BAC transgenic mice, has simplified the design of in vivo approaches for the analysis of gene expression and function in the brain. BAC transgenic mice carrying an exogenous 150 kb DNA sequence containing the Nurr1 promoter directly followed by the Tau green (TG) gene are being generated. The exogenous DNA, will be randomly integrated in the genome when injected into oocytes. As the carrying capacity of BACs is several hundred kilobases, and an average mammalian gene is <50kb, we have been able to insert the entire promoter region of the Nurr1 gene (as compared to other carrying vectors allowing only 10-15 kb inserts). In most cases, large genomic DNA fragments are expressed independently of the site of integration, and interference from other nearby sites in the genome is minimized. In these transgenic mice, Tau green expression will be driven by any elements present in the cell that activate the Nurr1 promoter. As a result all Nurr1 positive cells in these mice will also be Tau Green positive. These mice will be used in our laboratory to conduct several anatomical/functional studies in which mapping/visualization of the Nurr1 system is necessary.
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