TAMM-HORSFALL GENE:MODEL FOR KIDNEY SPECIFIC EXPRESSION

TAMM-HORSFALL 基因：肾脏特异性表达模型

• 批准号: 3246443
• 负责人: VIKAS P SUKHATME
• 金额: $ 24.72万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-05-01 至 1997-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3246443
• 关键词: DNA footprinting; Retroviridae; animal tissue; developmental genetics; gene expression; genetic mapping; genetic promoter element; genetic regulatory element; genetic transcription; genetically modified animals; human genetic material tag; human tissue; kidney; kidney disorder; laboratory mouse; laboratory rat; molecular cloning; nucleic acid sequence; tissue /cell culture; transcription factor; transfection

There has been little progress in identifying molecular events of import in renal organogenesis or in the related problem of defining the basis for kidney specific gene expression. This application proposes a program of studies whose long-term goal is to isolate genes encoding transcription factors which regulate gene expression in the kidney. Our approach utilizes a marker gene, the Tamm-Horsfall (TH) gene, that is unique to the kidney and is highly conserved in expression pattern and sequence in different mammalian species. Our aims are to delineate cis sequences and clone transcription factors regulating TH expression in the kidney. We intend to use diverse cellular and molecular methodologies to answer this question. These approaches include: transgenic mice, retroviral infection into embryonic kidney explants, cell culture transfection, DNAse I hypersensitive site mapping, gel shift analysis, DNAse I footprinting, in vitro transcription and expression cloning for transcription factor genes. These studies will (1) lead to an understanding of how gene expression is modulated in the kidney, (2) identify proteins of importance in kidney differentiation and growth with particular emphasis on the distal nephron where THP expression occurs, and (3) possibly provide novel insights into renal disease processes due to nephron injury or abnormal development.

在识别重要分子事件方面进展甚微 在肾器官发生或定义基础的相关问题中 用于肾脏特异性基因表达。 该应用程序提出了一个程序 长期目标是分离编码基因的研究 调节肾脏基因表达的转录因子。 我们的 方法利用标记基因，Tamm-Horsfall (TH) 基因，即 肾脏独有，表达模式高度保守 不同哺乳动物物种中的序列。 我们的目标是描绘顺 调节TH表达的序列和克隆转录因子 肾。 我们打算使用不同的细胞和分子方法来 回答这个问题。 这些方法包括：转基因小鼠、 逆转录病毒感染胚胎肾外植体、细胞培养 转染、DNAse I 超敏位点定位、凝胶位移分析、 DNAse I 足迹、体外转录和表达克隆 转录因子基因。 这些研究将（1）导致 了解肾脏中基因表达的调节方式，(2) 鉴定在肾脏分化和生长中重要的蛋白质 特别强调发生 THP 表达的远端肾单位， (3) 可能为肾脏疾病过程提供新的见解 肾单位损伤或发育异常。