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.