CRE Driver Strain Resources

CRE 驾驶员应变资源

• 批准号: 10450123
• 负责人: Stephen A Murray
• 金额: $ 66.19万
• 依托单位: JACKSON LABORATORY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-09 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10450123
• 关键词: Alleles; CRISPR/Cas technology; Catalogs; Characteristics; Collection; Communities; Community Outreach; Computer software; Cre driver; Custom; Data; Data Reporting; Databases; Development; Enterobacteria phage P1 Cre recombinase; Gene Targeting; Generations; Genes; Genetic; Genome; Goals; Informatics; Infrastructure; Insertional Mutagenesis; Lethal Genes; Literature; LoxP-flanked allele; Methods; Modeling; Mosaicism; Mouse Strains; Mus; Mutagenesis; Phase; Positioning Attribute; Public Health; Reporting; Research Personnel; Resource Informatics; Resources; Scientist; Services; Source; Specificity; System; Technology; The Jackson Laboratory; Tissues; Toxic effect; Transgenes; Transgenic Organisms; Validation; Variant; Work; base; bioinformatics tool; cell type; complement resource; data curation; data dissemination; experimental study; gene function; genome editing; human disease; human model; improved; informatics infrastructure; integration site; mouse genome; programs; recombinase; repository; stem cells; success; tool; web-based tool

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.

项目摘要/摘要 大规模的小鼠基因靶向项目，例如Komp，Eucomm，Norcomm和Tigm（统称为 IKMC），已经向科学界传达了大量有条件的Loxp flanke等位基因。 由于Komp2之类的程序旋转这些干细胞的努力，现在可以使用其中许多 资源进入活鼠。当与CRE等位基因结合使用时，该系统允许研究人员询问基因 以时间特定和组织特定方式通过精确缺失功能。利用这一点 IKMC资源将要求一套大量，多样化的特征良好的CRE驾驶员线可用于 世界各地的研究人员。不幸的是，目前，大多数现有的CRE驱动鼠标菌株不是 可从公共存储库获得，直到最近，还没有提议容纳的单个数据库 有关科学界可用的CRE驾驶员应变功能的全面信息。 虽然近年来可用菌株的目录已经增长，但仍然存在很大的差距，限制了我们的 能够在某些组织类型中剖析基因功能。此外，尽管那些正在发展的人都尽了最大的努力 新的CRE线，CRE活动的保真度并不总是理想的。在各种CRE中报告了许多困难 线，包括目标组织/细胞类型中的镶嵌或不完全缺失，活动不一致，表达 非目标组织，插入诱变和/或与CRE相关的毒性。通常，这些数据未报告 或潜在用户以及过去几年我们的工作表明，大多数CRE 线显示目标活动。该项目的总体目标是开发和分发全面的CRE 向科学界造成资源和信息。新资源将基于 杰克逊实验室（JAX）CRE存储库，其中包括分布和扩展特征 CRE驱动线和毛虫，它利用了小鼠基因组的信息基础设施 提供信息的信息，以提供CRE驱动器应变及其功能的数据库。为了补充这些资源， 该建议还试图进口一套扩展的CRE驾驶员应变，以填补我们的收藏中的空白，并且 有可能替代因关闭目标活动而混淆的关键菌株。在一起，这些将提供 CRE驱动器工具应变及其信息的全面来源的社区。

项目成果

Functional humanization of immunoglobulin heavy constant gamma 1 Fc domain human FCGRT transgenic mice.

• 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