BAC Transgenic Mice Encoding Tau Green Through the Nurr1

近年来，工程细菌人工染色体（BAC）方法的发展，以及BAC转基因小鼠的高效生产，简化了体内方法的设计，用于分析基因在大脑中的表达和功能。BAC转基因小鼠携带外源150 kb DNA序列，该序列包含Nurr1启动子，直接跟随Tau绿（TG）基因。外源DNA在注入卵母细胞时随机整合到基因组中。由于BACs的携带能力是几百个碱基，我们能够插入150 Kb的DNA片段重叠Nurr1基因（相比之下，其他携带载体只允许10-15 Kb的插入）。

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 have been generated. The exogenous DNA, was randomly integrated in the genome when injected into oocytes. As the carrying capacity of BACs is several hundred kilobases, we were able to insert a 150 Kb DNA fragment overlapping the Nurr1 gene (as compared to other carrying vectors allowing only 10-15 kb inserts). In these transgenic mice, Tau green expression was expressed only in the olfactory bulb, and absent in other brain areas known to express Nurr1. This data suggests that the BAC (containing the Nurr1 promoter) used in this study is lacking some of the regulatory elements necessary for driving TG expression in brain regions other than the olfactory bulb. We are currently developing additional BAC transgenic mice, for mapping/visualizing the midbrain dopaminergic system. These mice will be used in our laboratory to conduct several anatomical/functional studies in which mapping/visualization of the Nurr1/midbrain dopaminergic system is necessary.