...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Glia >GFAP promoter elements required for region-specific and astrocyte-specific expression
【24h】

GFAP promoter elements required for region-specific and astrocyte-specific expression

机译：区域特异性和星形胶质细胞特异性表达所需的GFAP启动子元件

获取原文
获取原文并翻译 | 示例
   

获取外文期刊封面封底 >>

       
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Glial fibrillary acidic protein (GFAP) is the major intermediate filament protein in astrocytes, one of the most abundant cell types in the vertebrate central nervous system (CNS). Transcriptional regulation of GFAP is of interest because of its astrocyte-specificity and its upregulation during development and CNS injury. A 2.2 kb human GFAP promoter, gfa2, has been found to express in astrocytes throughout the CNS. In contrast, we recently found that the 448 bp gfa28 promoter expresses in only restricted CNS regions, and is active in neurons as well as astrocytes. In the present study we have used transgenic mice to investigate which DNA regions deleted from gfa2 in the formation of gfa28 are responsible for these differences. We have found that a 55 bp segment spanning bp - 1488 to - 1434 with respect to the RNA start site contains region-specific elements and that a 45 bp sequence spanning bp - 1443 to - 1399 is required for silencing expression in neurons. These data also further confirm the heterogeneity of astrocytes and neurons in the activation and repression of the GFA-P gene, respectively. These studies also generated a novel 681 bp GFAP promoter, gfaABC(1)D, that has essentially the same expression pattern as the 2210 bp gfa2 promoter, and about twofold greater activity, recommending it for gene targeting applications in which size matters. In addition, a 681 bp gfaABC(1)(mC(1.1))D variant was generated that could limit expression of transgenes to astrocytes in the dorsal and caudal cortex, hippocampus and caudal vermis of the cerebellum. (C) 2008 Wiley-Liss, Inc.
机译：胶质纤维酸性蛋白（GFAP）是星形胶质细胞中的主要中间丝蛋白，星形胶质细胞是脊椎动物中枢神经系统（CNS）中最丰富的细胞类型之一。 GFAP的转录调控是令人感兴趣的，因为它的星形胶质细胞特异性及其在发育和中枢神经系统损伤期间的上调。已发现在整个CNS的星形胶质细胞中表达2.2 kb的人类GFAP启动子gfa2。相反，我们最近发现448 bp gfa28启动子仅在受限的CNS区表达，并在神经元和星形胶质细胞中有活性。在本研究中，我们已使用转基因小鼠研究了gfa28形成中从gfa2缺失的DNA区域是造成这些差异的原因。我们已经发现，相对于RNA起始位点而言，跨度介于-1488至1434 bp之间的55 bp片段包含区域特异性元件，而沉默于神经元表达所需的跨度介于-1443至1399 bp之间的45 bp序列。这些数据还进一步证实了星形胶质细胞和神经元在GFA-P基因的激活和抑制中的异质性。这些研究还产生了一个新的681 bp GFAP启动子gfaABC（1）D，该启动子具有与2210 bp gfa2启动子基本相同的表达模式，并具有大约两倍的活性，因此建议将其用于大小相关的基因靶向应用。此外，生成了一个681 bp的gfaABC（1）（mC（1.1））D变体，该变体可能将转基因的表达限制在小脑的背和尾皮质，海马和尾ver星形胶质细胞中。 （C）2008 Wiley-Liss，Inc.

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号