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中文摘要
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项目摘要/摘要 大规模的小鼠基因打靶项目,如KOMP、EUCOMM、NorCOMM和TIGM(统称为 已经向科学界提供了大量条件就绪的loxP侧翼等位基因。 由于KOMP2等项目的努力,这些干细胞中的许多现在都可以使用 将资源注入活老鼠体内。当与Cre等位基因结合时,该系统允许研究人员询问基因 以特定时间和特定组织的方式通过精确删除发挥作用。利用这一点 IKMC资源将需要大量、多样化、具有良好特性的CRE驱动程序系列可用来 世界各地的研究人员。不幸的是,目前大多数现有的Cre驱动鼠品系都不是 可从公共存储库获得,直到最近,还没有一个数据库提议存储 科学界可获得的有关Cre驱动株功能的全面信息。 虽然近年来可用菌株的目录有所增加,但仍有显著的差距限制了我们的 分析某些组织类型的基因功能的能力。此外,尽管发展中国家尽了最大努力 新的Cre品系,Cre活动的保真度并不总是理想的。据报道,在各种CRE中存在许多困难 包括目标组织/细胞类型中的镶嵌或不完全缺失、不一致的活性、在 非靶组织、插入突变和/或CRE相关毒性。通常,这些数据不会被报告 或对潜在用户可用,而我们过去几年的工作表明,大多数CRE 线条显示目标活动。该项目的总体目标是开发和分发全面的CRE 将资源和信息提供给科学界。新的资源将建立在成功的 杰克逊实验室(JAX)CRE资源库,包括分发和扩展表征 Cre驱动程序系列,以及利用Mouse Genome的信息学基础设施的CrePortal. 信息学提供Cre驱动菌株及其功能的数据库。为了补充这些资源, 这项建议还寻求进口一套扩大的Cre驱动菌株,以填补我们收集和 有可能取代因偏离目标活性而混乱的关键菌株。总而言之,这些将提供 社区中有一个全面的CRE驱动程序工具系列及其信息来源。
英文摘要
PROJECT SUMMARY/ABSTRACT Large-scale mouse gene targeting projects, such as KOMP, EUCOMM, NorCOMM, and TIGM (collectively, the IKMC), have delivered a vast number of conditional-ready loxP-flanked alleles to the scientific community. Many of these are now available thanks to the efforts of programs such as KOMP2 to turn these stem cell resources into live mice. When combined with a Cre allele, this system allows investigators to interrogate gene function through precise deletion in a temporally specific and tissue specific manner. To capitalize on this IKMC resource will require that a large, diverse set of well-characterized Cre driver lines are available to researchers around the world. Unfortunately, at present, most existing Cre driver mouse strains are not available from public repositories and until recently, there was no single database that proposed to house comprehensive information about the functionality of Cre driver strains available to the scientific community. While the catalog of available strains has grown in recent years, there are still significant gaps that limit our ability to dissect gene function in certain tissue types. Moreover, despite the best efforts of those developing new Cre lines, the fidelity of Cre activity is not always ideal. Many difficulties have been reported in various Cre lines, including mosaic or incomplete deletion in a target tissue/cell type, inconsistent activity, expression in non-target tissues, insertional mutagenesis and/or Cre-related toxicity. Frequently, these data are not reported or available to the potential user, and our work over the past several years has shown that a majority of Cre lines display off target activity. The overall goal of this project is to develop and distribute comprehensive Cre strain resources and information to the scientific community. The new resources will build upon the success of The Jackson Laboratory (JAX) Cre Repository, which includes both distribution and extended characterization of Cre driver lines, and the CrePortal, which leverages the informatics infrastructure of Mouse Genome Informatics to provide a database of Cre driver strains and their functionality. To complement these resources, this proposal also seeks to import an expanded set of Cre driver strains that will fill gaps in our collection and potentially replace critical strains that are confounded by off target activity. Together, these will provide the community with a comprehensive source of Cre driver tool strains and information about them.
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DOI: 10.1080/19420862.2020.1829334
发表时间: 2020-01
期刊: mAbs
影响因子: 5.3
作者: [Low BE, Christianson GJ, Lowell E, Qin W, Wiles MV]
通讯作者: Wiles MV
Preclinical Mouse Model Core
  • 批准号:
    10668764
  • 项目类别:
  • 资助金额:
    $66.97万
  • 财政年份:
    2023
  • 负责人:
    Stephen A Murray
  • 依托单位:
Disease Modeling Unit
  • 批准号:
    10251358
  • 项目类别:
  • 资助金额:
    $124.96万
  • 财政年份:
    2020
  • 负责人:
    Stephen A Murray
  • 依托单位:
Disease Modeling Unit
  • 批准号:
    10469586
  • 项目类别:
  • 资助金额:
    $108.39万
  • 财政年份:
    2020
  • 负责人:
    Stephen A Murray
  • 依托单位:
Animal Model Production Section
  • 批准号:
    10450129
  • 项目类别:
  • 资助金额:
    $4.43万
  • 财政年份:
    2018
  • 负责人:
    Stephen A Murray
  • 依托单位:
海外基金