These floxed mutant mice possess loxP sites flanking exon 3 of the Nr3c1 gene. This strain may be useful for generating conditional mutations in applications related to the study of the role played by Nr3c1 in development, metabolism, and immune responses.
Jonathan D Ashwell, Nat Cancer Inst/Nat Inst Health NCI/NIH
These GRfl/fl mutant mice possess loxP sites flanking exon 3 of the nuclear receptor subfamily 3, group C, member 1 (Nr3c1) gene. Nr3c1 encodes the glucocorticoid receptor which regulates genes involved in development, metabolism, and immune response by binding to cortisol and other steroid hormones. Mice that are homozygous for this allele are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exon 3 deleted in the cre-expressing tissues. Widespread deletion of GR results in perinatal lethality due to failure to produce surfactant.
When bred to B6.Cg-Tg(Lck-cre)548Jxm/J mice (Stock No. 003802) expressing thymocyte-specific cre, the resulting offspring exhibit compromised immune responses due to altered selection of the antigen specific TCR repertoire.
A targeting vector was designed to insert a loxP site upstream of exon 3 and a second loxP site downstream of exon 3, followed by a frt-flanked neomycin resistance (neo) cassette, of the nuclear receptor subfamily 3, group C, member 1 (Nr3c1) gene. The construct was electroporated into 129/B6 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and resulting chimeric mice were bred to C57BL/6J mice. Offspring were bred with Flp transgenic mice, on a C57BL/6 background, to delete the neo cassette, and progeny were crossed to remove the Flp-expressing transgene. The donating investigator reported that these GRfl/fl mice were backcrossed to C57BL/6J mice for at least 6 generations (see SNP note below). Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.
A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 4 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.
|Allele Name||targeted mutation 1.1, Jonathan D Ashwell|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Gene Symbol and Name||Nr3c1, nuclear receptor subfamily 3, group C, member 1|
|Strain of Origin||129 and C57BL/6|
|Molecular Note||A targeting vector was designed to insert a loxP site upstream of exon 3 and a second loxP site downstream of exon 3, followed by a frt-flanked neomycin resistance (neo) cassette. Flp-mediated recombination remvoed the neo cassette.|
When maintaining a live colony, homozygous mice may be bred together.
When using the GRfl mouse strain in a publication, please cite the originating article(s) and include JAX stock #021021 in your Materials and Methods section.