Cre alleles from CREATE (coordination of resources for conditional expression of mutated mouse alleles)

Conditional knockout models have greatly contributed to studies into gene function and disease processess by allowing the inactivation of gene function in specific tissues and/or developmental timepoints in mice. This is generally achieved by flanking a critical gene exon with loxP sites (e.g. a "floxed" allele) in such a manner that does not interfere with gene transcription. In the presence of the Cre recombinase, recombination occurs between the loxP sites resulting in the removal of the critical gene segment and inactivating the gene.

The full potential of conditional knockout models mice is only realized with the availability of well characterised mouse lines expressing Cre-recombinase in tissue, organ and cell type-specific patterns. This is best achieved by substituting a Cre recombinase expression vector for the coding exons of genes that have the desired spatial and temporal restricted expression. The promoter and other genomic elements that control expression of the native gene will "drive" expression of the Cre recombinase instead. These "Cre Driver" mice can then be bred with mice carrying a floxed allele to generate the desired conditional knockout. Variants of Cre Driver mice allow temporal control of Cre activity by employing fusion proteins of the Cre enzyme with modified versions of the ligand binding domains of the estrogen receptor that are responsive to the synthetic ligand tamoxifen.