Parental origin of transgene determines recombination efficiency in GFAP-creERT2 mice

The Cre-loxP system is a powerful tool for spatial and temporal genetic manipulations. However, the system is prone to several limitations and caveats with respect to variable expression and recombination in unintended cell types. Using one of the most widely used astrocyte Cre lines, hGFAP-creERT2 ((GFAP-cre/ERT2)505Fmv/J), we found that parental origin of the hGFAP-creERT2 transgene is a determinant of recombination efficiency. Recombination was robust in animals with paternally inherited hGFAP-creERT2. However, animals with maternally inherited Cre exhibited little to no recombination. This result was recapitulated using female hGFAP-creERT2 mice procured directly from Jackson Laboratory. We did not observe transgenerational suppression of Cre recombination in maternally inherited hGFAP-CreERT2. These data highlight the need for careful planning and documentation of breeding schemes when working with Cre mice.