Expression mapping of tetracycline-responsive prion protein promoter: Digital atlasing for generating cell-specific disease models
Expression mapping of tetracycline-responsive prion protein promoter: Digital atlasing for generating cell-specific disease models
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DOI：
10.1016/j.neuroimage.2006.05.055
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发表时间：
2006-11-01
期刊：
影响因子：
5.7
通讯作者：
Bjaalie, Jan G.
中科院分区：
文献类型：
--
作者：
Boy, Jana;Leergaard, Trygve B.;Bjaalie, Jan G.
提出了一个数字图谱系统，该系统允许通过大量的组织学切片以细胞分辨率绘制分子表达模式。使用该系统，我们绘制了双转基因小鼠中由四环素响应朊病毒蛋白启动子驱动的 LacZ 报告基因编码的独特标记的分布图。目的是评估该启动子小鼠系针对特定大脑区域的感兴趣基因的适用性，这对于构建诱导性转基因疾病模型至关重要。在对启动子表达进行可视化处理后，对切片进行复染以同时显示细胞结构。每隔 200 点通过小鼠大脑收集覆盖整个冠状切片的高分辨率马赛克图像。基于网络的应用程序提供对定制虚拟显微镜工具的访问，用于在切片图像内和跨切片图像进行查看和导航。对于每个截面图像，定义了标准图谱中最近的截面，并插入了关键结构和区域的注释。使用分布模式对标记细胞进行假定分类，然后使用细胞大小和形状作为与遗留数据进行比较的参数。随后的结果包括该启动子在小脑的假定神经胶质细胞（而不是浦肯野细胞）、黑质的假定神经胶质细胞、苍白球神经胶质细胞或中间神经元以及海马的不同细胞层和区域中的表达。该研究作为数据库资源的先驱，允许评估不同启动子小鼠品系用于生成疾病模型的适用性。 (c) 2006 Elsevier Inc. 保留所有权利。
present a digital atlas system that allows mapping of molecular expression patterns at cellular resolution through large series of histological sections. Using this system, we have mapped the distribution of a distinct marker, encoded by the LacZ reporter gene driven by the tetracycline-responsive prion protein promoter in double transgenic mice. The purpose is to evaluate the suitability of this promoter mouse line for targeting genes of interest to specific brain regions, essential for construction of inducible transgenic disease models. Following processing to visualize the promoter expression, sections were counterstained to simultaneously display cytoarchitectonics. High-resolution mosaic images covering entire coronal sections were collected through the mouse brain at intervals of 200 pm. A web-based application provides access to a customized virtual microscopy tool for viewing and navigation within and across the section images. For each section image, the nearest section in a standard atlas is defined, and annotations of key structures and regions inserted. Putative categorization of labeled cells was performed with use of distribution patterns, followed by cell size and shape, as parameters that were compared to legacy data. Among the ensuing results were expression of this promoter in putative glial cells in the cerebellum (and not in Purkinje cells), in putative glial cells in the substantia nigra, in pallidal glial cells or interneurons, and in distinct cell layers and regions of the hippocampus. The study serves as a precursor for a database resource allowing evaluation of the suitability of different promoter mouse lines for generating disease models. (c) 2006 Elsevier Inc. All rights reserved.