A New Tool for Reproductive Biology: Exploring Recombinases for Conditional Mutagenesis.

Conditional mutagenesis in mouse is a powerful tool for examining effects of stage-specific gene regulation and for studying gene function in cases where critical early developmental expression causes gene knockouts to be lethal. Conditional genotypes are "knocked-out" at the site of interest in a spatial and temporal manner, determined by the driver/promoter element of the recombinase containing transgene or knock-in allele used. Many new conditional-ready targeted mutations are being made through the efforts of the International Knockout Mouse Consortium (www.knockoutmouse.org). To maximize the utility of these new mutations, a companion set of specific cre driver mice is needed ("cre" is used here to stand-in for all variations of recombinase constructs). Fundamental to choosing cre-bearing strains for mating with these mutants and to interpreting phenotypes from conditional genotypes is the need to understand the temporal and spatial distribution of cre recombinase expression and specificity. Thus, for example, it is important to know that a conditional knockout is gonad-specific or has wider tissue specificity that could secondarily affect reproductive traits. We have built a Recombinase (cre) Portal as a central access point to cre expression and specificity data (www.creportal.org) to aid researchers using conditional mutagenesis. For cre-containing transgenes or knock-in alleles, key data include the molecular description of the cre construct, the driver/promoter element, whether the construct is inducible or not, publications, and availability of the cre-bearing mice through a public repository. Of particular importance are the curated annotations (with images, when available) of the tissues, specific structures, and ages assayed that define the specificity of the cre transgene or knock-in allele. Recombinase transgenes or knock-ins can be searched by specificity in a particular anatomical system or by specific promoter/driver (http://www.creportal.org). Nomenclature searches can be done by transgene or knock-in symbol or synonym. Downloads and views of complete recombinase data summaries are also provided. As of March 1, 2010, there are over 1,160 unique recombinase-containing transgenes and knock-in alleles cataloged in the Cre Recombinase Portal. We welcome comments on www.creportal.org and user contributions on their experiences with specific cre constructs. The Recombinase (cre) Portal project is funded by NIH grants HG000330 and HD033745 and EU grant HEALTH-F4-2009-223487. (poster)