FVB.B6-Nfe2l2^tm1.1Sred/JwkimJ

Stock number: 034617
Product name: FVB.Nrf2^flox
Research areas: Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Research Tools

Description

Nrf2^flox mice possess loxP sites flanking exon 5 of the Nfe2l2 gene on a congenic FVB/NJ background. 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.

Of note, The Jackson Laboratory Repository also offers Nrf2^flox mice on a C57BL/6 genetic background (Stock No. 025433).

Detailed description

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. The phenotype summarized below is for the parental line: Nrf2^flox mice on a C57BL/6 genetic background (Stock No. 025433). It should be noted that the phenotype of this FVB/NJ-congenic Nrf2^flox line (Stock No. 034617) could vary from that of the parental line from which it was derived.

The targeted Nfe2l2 gene, also known as Nrf2, encodes a transcription factor that is involved in oxidative stress response. These Nrf2^flox mice possess loxP sites on either side of exon 5 which encodes the DNA binding domain. Mice homozygous for this Nrf2^flox 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).

Development

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 were 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 ten generations prior to donating the line to The Jackson Laboratory in 2016 as Stock No. 025433.

In 2016, Dr. Jung-Whan Kim purchased some Stock No. 025433 animals (~N11 onto C57BL/6) and then backcrossed them ten generations to FVB/NJ inbred mice (from Stock No. 001800). The resulting FVB/NJ-congenic strain is called FVB.Nrf2^flox. Of note, the donating investigator reports that, at least once during backcrossing, a Nrf2^flox female was bred to an FVB/NJ inbred male (thus the Y chromosome of the congenic strain is of FVB/NJ origin). In 2020, FVB.Nrf2^flox males (white coat color) were sent to The Jackson Laboratory Repository as Stock No. 034617. Upon arrival, males were used to cryopreserve sperm. To establish our live colony, an aliquot of frozen sperm was used to fertilize FVB/NJ oocytes.

Allele

Symbol: Nfe2l2^tm1.1Sred
Name: targeted mutation 1.1, Sekhar P Reddy
MGI accession ID: MGI:5463890
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Synonyms: Nrf2^f; Nrf2^flox
Marker symbol: Nfe2l2
Marker name: nuclear factor, erythroid derived 2, like 2
Marker synonyms: IMDDHH; Nrf2; Nrf-2
Chromosome: 2
Strain of origin: C57BL/6J
Molecular note: Exon 5 was floxed. Flp-mediated recombination removed the FRT-flanked neo cassette.