B6.Cg-Tnfrsf11a^tm1.1Irw/J

Stock number: 027495
Product name: RANK^F/F
Research areas: Cell Biology Research, Research Tools

Description

RANK^F/F floxed mice may be useful for studying tissue specific RANKL-RANK signaling.

Detailed description

RANK^F/F floxed mice possess loxP sites flanking exons 2-3 of the tumor necrosis factor receptor superfamily, member 11a, NFKB activator (Tnfrsf11a) gene. Tnfrsf11a encodes RANK (Receptor Activator of Nuclear Factor κB) and is expressed in a variety of tissues including skeletal muscle, thymus, liver, colon, small intestine, adrenal gland, osteoclast, mammary gland epithelial cells, prostate, vascular cells, and pancreas. RANK signaling through its ligand, RANKL, has an important role lymph node development, osteoclast differentiation, medullary thymic epithelial cell differentiation, body temperature regulation, milk production by lactating mammary epithelial cells, and intestinal M cell differentiation. 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 exons 2-3 deleted in the cre-expressing tissues.

For example, when bred to B6.Cg-Tg(Vil-cre)997Gum/J transgenic mice (Stock No. 004586) expressing Cre Recombinase in the intestinal epithelium, resulting RANK^ΔIEC mice lack RANK expression in crypt enterocytes and completely lack intestinal M cells. They display defects in development of secretory IgA in the intestine.

Development

A targeting vector was designed to insert a frt-flanked neomycin resistance (neo) cassette, followed by a loxP site, upstream of exon 2, and a second loxP site downstream of exon 3 of the tumor necrosis factor receptor superfamily, member 11a, NFKB activator (Tnfrsf11a) gene. The construct was electroporated into (C57BL/6NTac x 129S6/SvEvTac)F1-derived iTL BA1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and resulting chimeric mice were bred with Flp transgenic mice on a C57BL/6 background to delete the neo cassette. Progeny were crossed to remove the Flp-expressing transgene, and the resulting RANK^F/F mice were bred to C57BL/6 mice for many generations by the donating lab to generate a congenic colony (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

Symbol: Tnfrsf11a^tm1.1Irw
Name: targeted mutation 1.1, Ifor R Williams
MGI accession ID: MGI:5629957
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed)
Marker symbol: Tnfrsf11a
Marker name: tumor necrosis factor receptor superfamily, member 11a, NFKB activator
Chromosome: 1
Strain of origin: (C57BL/6NTac x 129S6/SvEvTac)F1
Molecular note: Exons 2 and 3 were floxed. Flp-mediated recombination removed the FRT-flanked selection cassette inserted upstream of exon 2.