B6.129-Hsd11b2^tm1.1Mzz/RhrsJ

Stock number: 036772
Product name: Hsd11b2^flox
Research areas: Cancer Research, Research Tools

Description

Hsd11b2^flox/flox mice have loxP sites flanking exons 1-5 of the Hsd11b2 gene. This strain is useful for studying the role of glucocorticoid activity on tumor growth inhibition.

Detailed description

Hsd11b2^flox/flox mice have loxP sites flanking exons 1-5 of the hydroxysteroid 11-beta dehydrogenase 2 (Hsd11b2) gene. Hsd11b2 encodes an enzyme that converts the glucocorticoid cortisol to the inactive metabolite. Increased 11βHSD2 expression has also been seen in human colonic adenomas and intestinal adenomas from Apc^+/min mice (Stock No. 002020) correlating with increased COX-2 expression and activity. Homozygous mice are viable and fertile. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exons 1-5 deleted in cre-expressing tissues.



When bred to Villin-cre mice (Stock No. 004586), with cre expression in intestinal epithelial cells, and subsequently bred to Apc^+/min mice, resulting Vil-HSD2^-/- Apc^+/min mice have a decrease in adenoma initiation and growth, as compared to Apc^+/min mice, as a result of increased tumor intracellular active glucocorticoids. They also exhibit attenuation of COX-2 expression, increased cell-cycle arrest, and inhibition of mTOR signaling.

Development

A targeting vector was designed to insert a loxP site upstream of exon 1 of the hydroxysteroid 11-beta dehydrogenase 2 (Hsd11b2) gene. A frt-flanked neomycin resistance (neo) cassette, followed by a second loxP site was inserted downstream of exon 5. The construct was electroporated into 129-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and resulting chimeric males were bred with C57BL/6 females. Subsequently, offspring were bred to ROSA26::FLPe mice (Stock No. 003946) mice to remove the neo cassette. Progeny were crossed to remove the FLPe-expressing transgene and resulting Hsd11b2^flox mice were bred to C57BL/6J mice (Stock No. 00664) for at least 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.

Allele

Symbol: Hsd11b2^tm1.1Mzz
Name: targeted mutation 1.1, Ming-Zhi Zhang
MGI accession ID: MGI:5547496
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Synonyms: Hsd11b2^flox
Marker symbol: Hsd11b2
Marker name: hydroxysteroid 11-beta dehydrogenase 2
Marker synonyms: 11(beta)-HSD2; 11HSD2; AME; AME1; HSD11K; HSD2; SDR9C3
Chromosome: 8
Strain of origin: 129
Molecular note: A loxP site was inserted upstream of exon 1. An FRT-flanked neomycin resistance cassette with a 3' loxP site was inserted downstream of exon 5. Flp-mediated recombination removed the neomycin resistance cassette and left exons 1 through 5 floxed.