Nrf2flox mice possess loxP sites flanking exon 5 of the Nfe2l2 gene. Exposure to Cre recombinase removes the floxed sequence - creating a null allele. This strain may be useful for generating conditional mutations in applications related to wound repair and inflammation.
Sekhar Reddy, University of Illinois College of Medicine
Shyam S Biswal, Johns Hopkins Bloomberg School of Public Health
The targeted Nfe2l2 gene, also known as Nrf2, encodes a transcription factor that is involved in oxidative stress response. These Nrf2flox mice possess loxP sites on either side of exon 5 which encodes the DNA binding domain. Mice homozygous for this Nrf2flox allele are viable and fertile. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exon 5 deleted in the cre-expressing tissues. Removal of the floxed sequence creates a null allele.
For example, when bred to a strain with Cre recombinase expression in lung Clara cells (Scgb1a1-cre), this mutant mouse strain may be useful in studies of lung injury and inflammation (Reddy et al. 2011).
Furthermore, when crossed to a retinal-specifc Cre expressing strain, such as Six3-cre (Stock No. 019755) or an endothelial-specific Cre such as Cdh5-cre (Stock No. 006137), the deletion of Nrf2 impairs the revascularization of the retina following oxygen-induced retinopathy (OIR) (Wei et al. 2015).
A targeting vector containing a PGK-Neo selection cassette was utilized in the construction of this mutant. A FRT site, a loxP site and this selection cassette followed by a second FRT site and a second loxP site was inserted downstream of exon 5 of the targeted gene. Another loxP site was inserted upstream of exon 5. This construct was electroporated into unspecified C57BL/6-derived embryonic stem (ES) cells which were transiently transfected with a FLPe recombinase vector to remove the selection cassette. ES cells in which Cre recombination resulted in exon 5 being flanked by loxP sites were injected into blastocysts. Resulting chimeric animals were backcrossed to C57BL6/J mice for 10 generations. Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).
|Allele Name||targeted mutation 1.1, Sekhar P Reddy|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Allele Synonym(s)||Nrf2f; Nrf2flox|
|Gene Symbol and Name||Nfe2l2, nuclear factor, erythroid derived 2, like 2|
|Strain of Origin||C57BL/6J|
|Molecular Note||Exon 5 was floxed. Flp-mediated recombination removed the FRT-flanked neo cassette.|
When maintaining a live colony, these mice can be bred as homozygotes.
When using the Nrf2flox mouse strain in a publication, please cite the originating article(s) and include JAX stock #025433 in your Materials and Methods section.