Cre Driver Strain Resources

描述（由申请人提供）：大规模小鼠基因靶向项目，如KOMP、EUCOMM、NorCOMM和TIGM（统称为IKMC），有望为科学界提供大量条件就绪loxP侧翼等位基因。与携带Cre重组酶的小鼠交配的携带这种条件就绪等位基因的小鼠的后代将具有以空间和时间方式特异性敲除的等位基因，这取决于携带Cre的亲本中存在的构建体和驱动子。要利用这一IKMC资源，将需要一个大的，不同的一套良好的特点Cre驱动程序线提供给世界各地的研究人员。不幸的是，目前，大多数现有的Cre驱动小鼠品系不能从公共存储库中获得，直到最近，还没有一个数据库提出容纳有关科学界可用的Cre驱动品系功能的全面信息。此外，尽管开发新Cre系的人尽了最大努力，但Cre活性的保真度并不总是理想的。在各种Cre系中已经报道了许多困难，包括在靶组织/细胞类型中的嵌合或不完全缺失、不一致的活性、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，这些数据没有报告或提供给潜在的用户，我们的初步数据表明，绝大多数的Cre线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并向科学界分发全面的Cre菌株资源和信息。新资源将建立在杰克逊实验室（JAX）Cre知识库的成功基础上，该知识库包括Cre驱动程序线的分布和扩展表征，以及最近推出的CrePortal，它利用小鼠基因组信息学的信息学基础设施提供Cre驱动程序菌株及其功能的数据库。该提案旨在将这些原型努力扩展到更大，更强大的规模，并开发新的工具，以促进更容易构建新的Cre系。总之，这些将为社区提供一个全面的Cre驱动程序工具菌株和有关它们的信息。

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.