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.
(provided by applicant): The mouse is an invaluable tool for modeling human disease. The tremendous power of the mouse is due in part to our ability to manipulate its genome in a precise manner. This proposal seeks to leverage our mouse and informatic resources to enhance the value of mouse tool strains for the scientific community. Because of our position as a central resource utilized by thousands of scientists around the world, this project promises to have an important impact on the development of new models of human disease.
|Murray, Stephen A; Eppig, Janan T; Smedley, Damian et al. (2012) Beyond knockouts: cre resources for conditional mutagenesis. Mamm Genome 23:587-99|