Centre for Molecular Medicine and Therapeutics at the Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada V5Z4H4.
Proc Natl Acad Sci U S A. 2010 Sep 21;107(38):16589-94. doi: 10.1073/pnas.1009158107. Epub 2010 Aug 31.
The Pleiades Promoter Project integrates genomewide bioinformatics with large-scale knockin mouse production and histological examination of expression patterns to develop MiniPromoters and related tools designed to study and treat the brain by directed gene expression. Genes with brain expression patterns of interest are subjected to bioinformatic analysis to delineate candidate regulatory regions, which are then incorporated into a panel of compact human MiniPromoters to drive expression to brain regions and cell types of interest. Using single-copy, homologous-recombination "knockins" in embryonic stem cells, each MiniPromoter reporter is integrated immediately 5' of the Hprt locus in the mouse genome. MiniPromoter expression profiles are characterized in differentiation assays of the transgenic cells or in mouse brains following transgenic mouse production. Histological examination of adult brains, eyes, and spinal cords for reporter gene activity is coupled to costaining with cell-type-specific markers to define expression. The publicly available Pleiades MiniPromoter Project is a key resource to facilitate research on brain development and therapies.
昴宿星启动子项目将全基因组生物信息学与大规模基因敲入小鼠生产和组织学表达模式检查相结合，开发出小型启动子和相关工具，旨在通过定向基因表达来研究和治疗大脑。具有大脑表达模式的基因进行生物信息学分析，以描绘候选调控区域，然后将这些区域整合到一组紧凑的人类小型启动子中，以驱动对感兴趣的脑区和细胞类型的表达。使用胚胎干细胞中的单拷贝、同源重组“基因敲入”，每个小型启动子报告基因都立即整合到小鼠基因组中 Hprt 基因座的 5'端。在转基因细胞的分化实验或转基因小鼠产生后的小鼠大脑中，对小型启动子表达谱进行特征分析。报告基因活性的成年大脑、眼睛和脊髓的组织学检查与细胞类型特异性标志物的共染色相结合，以定义表达。公开可用的昴宿星小型启动子项目是促进大脑发育和治疗研究的关键资源。
