THE ROLE OF WNT SIGNALING IN DEVELOPMENT

WNT 信号传导在发育中的作用

• 批准号: 7561535
• 负责人: TADMIRI Rangachar VENKATESH
• 金额: $ 41.27万
• 依托单位: CITY COLLEGE OF NEW YORK
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7561535
• 关键词: A Mouse; B-Cell Development; Biological Process; Blood Vessels; Collaborations; Complex; Computer Retrieval of Information on Scientific Projects Database; Development; Disruption; Funding; Gene Targeting; Genes; Goals; Grant; Institution; Knock-out; Knockout Mice; Mus; Mutation; Pathway interactions; Pilot Projects; Request for Proposals; Research; Research Personnel; Research Project Grants; Research Proposals; Resource Sharing; Resources; Retinal; Role; Signal Pathway; Signal Transduction; Source; T-Cell Development; Techniques; Testing; Transgenic Mice; United States National Institutes of Health; base; insight; interest; knockout gene; mutant; receptor; tool

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a pilot proposal requesting funds to support collaborative research between three RCMI investigators with shared research interests. A central theme of the proposal is the use of mouse gene knockout studies to gain insights into the role of important signaling pathways during development. Gene disruption provides a powerful tool towards understanding complex biological processes. Transgenic mouse lines carrying single mutations in genes of interest will be generated using a new highly efficient Targeted gene trapping technique. These knockout lines will be used by each of the three investigators. The focus of the current research proposal will be to examine the role of Wnt signaling pathway during development. A mouse knockout line for the Kremen1, a gene which encodes an inhibitory receptor for the Wnt signaling pathway, has already been established and the initial studies will focus on phenotypic analyses of these mutant lines. Utilizing these krm1 mutants, the three investigators will test the basic hypothesis that loss of Krm1 function results in increased Wnt signaling leading to the following aberrant pathways: 1) retinal vascular development, 2) T cell development and 3) B cell development. Because of the expense of generating mouse knockouts, this is a very efficient and economical approach of sharing resources and promoting collaboration among RCMI investigators. It is expected that the results from the pilot project will be the basis of new research grants and contribute significantly towards the overall goals of the RCMI.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 这是一项试点提案，请求资金支持三名具有共同研究兴趣的 RCMI 研究人员之间的合作研究。该提案的中心主题是利用小鼠基因敲除研究来深入了解发育过程中重要信号通路的作用。 基因破坏为理解复杂的生物过程提供了强大的工具。 使用新的高效靶向基因捕获技术将产生携带感兴趣基因单突变的转基因小鼠品系。 这些淘汰线将由三名调查员中的每一位使用。 当前研究计划的重点是研究 Wnt 信号通路在发育过程中的作用。 Kremen1（一种编码 Wnt 信号通路抑制性受体的基因）的小鼠敲除系已经建立，初步研究将集中于这些突变系的表型分析。利用这些 krm1 突变体，三位研究人员将测试一个基本假设，即 Krm1 功能丧失会导致 Wnt 信号传导增加，从而导致以下异常途径：1) 视网膜血管发育，2) T 细胞发育和 3) B 细胞发育。由于产生小鼠基因敲除的费用很高，因此这是一种非常有效且经济的共享资源和促进 RCMI 研究人员之间合作的方法。 预计试点项目的结果将成为新研究资助的基础，并对 RCMI 的总体目标做出重大贡献。