Quality Control of Astrocyte-Directed Cre Transgenic Mice: The Benefits of a Direct Link Between Loss of Gene Expression and Reporter Activation

Cre recombinase activity for cell-type restricted deletion of floxed target genes (i.e., flanked by Cre recognition loxP-sites) is often measured by separate matings with recombination-activated reporter gene mice. Using a floxed Gja1 (Cx43) allele, we demonstrate the benefits of a direct link between reporter gene expression and target gene deletion to overcome critical limitations of the Cre/loxP system. The widely used human glial fibrillary acidic protein (hGFAP)-Cre transgene exhibits variable recombination activity and requires postexperimental validation. Such quality control is essential to correlate the extent of Cre-mediated Gja1 ablation with phenotypical alterations and to maintain the activity status of hGFAP-Cre in transgenic mouse colonies. We present several strategies to control for the fidelity of hGFAP-Cre mediated recombination. (C) 2008Wiley-Liss, lnc.