CRE Driver Strain Resources

项目总结/摘要 大规模的小鼠基因靶向项目，如KOMP、EUCOMM、NorCOMM和TIGM（统称为 IKMC）已经向科学界提供了大量的条件就绪loxP侧翼等位基因。 由于KOMP 2等项目的努力，其中许多干细胞现在都可以获得， 资源转化为活的老鼠。当与Cre等位基因结合时，该系统允许研究人员询问基因 以时间特异性和组织特异性方式通过精确缺失发挥作用。为了充分利用这种 IKMC资源将需要一个大的，不同的一套良好的特点Cre驱动程序线， 世界各地的研究人员。不幸的是，目前，大多数现有的Cre驱动小鼠品系不是 可从公共存储库，直到最近，没有一个单一的数据库，建议容纳 关于Cre驱动菌株功能的全面信息可供科学界使用。 虽然近年来可用菌株的目录有所增加，但仍然存在重大差距，限制了我们的研究。 在某些组织类型中剖析基因功能的能力。此外，尽管发展中国家尽了最大努力， 新的Cre系，Cre活性的保真度并不总是理想的。许多困难已报告在各种克雷 细胞系，包括靶组织/细胞类型中的镶嵌或不完全缺失、活性不一致、表达 非靶组织、插入诱变和/或Cre相关毒性。这些数据往往没有报告 或提供给潜在用户，我们在过去几年的工作表明，大多数Cre 线显示偏离目标的活动。该项目的总体目标是开发和分发综合的Cre 向科学界提供资源和信息。新的资源将建立在成功的基础上， 杰克逊实验室（JAX）Cre存储库，包括分发和扩展表征 Cre驱动程序线和CrePortal，它利用了小鼠基因组的信息学基础设施， 信息学提供Cre驱动程序菌株及其功能的数据库。为了补充这些资源， 该提案还寻求进口一套扩大的Cre驱动菌株，以填补我们收集的空白， 潜在地替代被脱靶活性混淆的关键菌株。总之，这些将提供 社区提供了一个全面的Cre驱动程序工具菌株源和有关它们的信息。

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.