Cre Driver Strain Resources

描述(由申请人提供)：大规模的小鼠基因靶向项目，如KOMP、EUCOMM、NorCOMM和TIGM(统称为IKMC)，承诺向科学界提供大量条件就绪的loxP侧翼等位基因。携带这种条件性准备好的等位基因的小鼠的后代，与携带Cre重组酶的小鼠交配，将拥有在空间和时间上被特定敲除的等位基因，这取决于携带Cre的亲本中存在的结构和驱动因素。为了利用这种IKMC资源，需要向世界各地的研究人员提供大量、多样化的、具有良好特性的CRE驱动程序系列。不幸的是，目前大多数现有的Cre驱动小鼠品系还不能从公共资源库中获得，直到最近，还没有一个数据库提议容纳科学界可用的关于Cre驱动品系功能的全面信息。此外，尽管那些开发新的CRE线路的人尽了最大努力，但CRE活动的保真度并不总是理想的。在不同的Cre系中已经报道了许多困难，包括靶组织/细胞类型中的镶嵌或不完全缺失，活性不一致，在非靶组织中的表达，和/或Cre相关的毒性。然而，在许多情况下，这些数据不会报告或提供给潜在用户，我们的初步数据表明，绝大多数Cre行表现出未报告或意外的删除活动。该项目的总体目标是开发和向科学界分发全面的CRE菌株资源和信息。新的资源将建立在杰克逊实验室(JAX)CRE储存库的成功基础上，该储存库包括CRE驱动程序系列的分发和扩展特性，以及最近推出的CrePortal，它利用老鼠基因组信息学的信息基础设施提供CRE驱动程序菌株及其功能的数据库。这项提议旨在将这两项原型努力扩展到更大、更强大的规模，并开发新的工具，以促进新的CRE线路的更容易建设。总而言之，这些将为社区提供全面的CRE驱动程序工具品系及其相关信息来源。

DESCRIPTION (provided by applicant): Large-scale mouse gene targeting projects, such as KOMP, EUCOMM, NorCOMM, and TIGM (collectively, the IKMC), promise to deliver a vast number of conditional-ready loxP-flanked alleles to the scientific community. Offspring of mice bearing such conditional-ready alleles, mated to Cre recombinase bearing mice, will harbor alleles that are specifically knocked-out in a spatial and temporal manner, dependent on the construct and driver present in the Cre-bearing parent. 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. 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, and/or Cre-related toxicity. In many cases, however, these data are not reported or available to the potential user, and our preliminary data suggests that the vast majority of Cre lines exhibit unreported or unexpected deletion 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 recently launched CrePortal, which leverages the informatics infrastructure of Mouse Genome Informatics to provide a database of Cre driver strains and their functionality. This proposal seeks to expand both of these prototypic efforts to a larger, more robust scale, and to develop novel tools to facilitate easier construction of new Cre lines. Together, these will provide the community with a comprehensive source of Cre driver tool strains and information about them.