Cre Driver Strain Resources

Cre 驱动应变资源

• 批准号: 8721071
• 负责人: Janan T. EPPIG
• 金额: $ 25万
• 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 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8721071
• 关键词: Age; Alleles; American; Bioinformatics; Canada; Cell Nucleus; Cell membrane; Cells; Characteristics; Communities; Data; Databases; Deposition; Development; Docking; ES Cell Line; European; Evaluation; Excision; Exhibits; Future; Gene Targeting; Genome; Genomics; Goals; Histocompatibility Testing; Housing; Informatics; Institutes; International; Knock-out; Knockout Mice; Laboratories; Mediating; Medicine; Modeling; Mouse Strains; Mus; Mutagenesis; Parents; Partner in relationship; Phenotype; Positioning Attribute; Publishing; Quality Control; Reagent; Reporter; Reporting; Research Infrastructure; Research Personnel; Resource Informatics; Resources; Scientist; Series; Shuttle Vectors; Site; Sorting - Cell Movement; Source; Texas; The Jackson Laboratory; Time; Tissues; Toxic effect; base; cell type; embryonic stem cell; human disease; insight; mouse genome; mutant; novel; offspring; recombinase; repository; research study; success; tool

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.

描述（由申请人提供）：大型小鼠基因靶向项目，例如Komp，Eucomm，Norcomm和Tigm（统称为IKMC），承诺将向科学界提供大量有条件的有条件的Loxp flankplanke等位基因。带有这种有条件的就绪等位基因的小鼠的后代与CRE重组酶轴承小鼠配对，将携带以空间和时间的方式被专门敲除的等位基因，取决于含有CRE的父母中的构建体和驱动器。为了利用这一IKMC资源，将要求全球研究人员可以使用一套大量的，多样化的CRE驾驶员线。不幸的是，目前，大多数现有的CRE驱动器鼠标菌株都无法从公共存储库中获得，直到最近，还没有提议提供有关科学界可用的CRE驾驶员应变功能的全面信息。此外，尽管那些开发新的CRE系列的人做出了最大的努力，但CRE活动的保真度并不总是理想的。在各种CRE系中报道了许多困难，包括目标组织/细胞类型中的镶嵌或不完全缺失，活性不一致，在非目标组织中的表达以及/或与CRE相关的毒性。但是，在许多情况下，这些数据尚未向潜在用户报告或可用，我们的初步数据表明，绝大多数CRE线都表现出未报告或意外的删除活动。该项目的总体目标是向科学界开发和分发全面的CRE应变资源和信息。新资源将基于杰克逊实验室（JAX）CRE存储库的成功，其中包括CRE驾驶员线的分布和扩展表征，以及最近发射的Creportal，该库利用了小鼠基因组信息学的信息学基础结构，以提供CRE驾驶员量的数据库及其功能及其功能。该提案旨在将这两种原型努力扩展到更大，更健壮的规模，并开发出新颖的工具，以促进更轻松的新CRE线路结构。这些将共同为社区提供全面的CRE驱动器工具应变及其信息。