B6.Cg-Tg(CDX2-Cre/ERT2)752Erf/J

Stock number: 022390
Product name: CDX2P-CreER^T2
Research areas: Cancer Research, Internal/Organ Research, Research Tools

Description

These mice express Cre-ER^T2 under the direction of the human caudal type homeo box 2 (CDX2) gene promoter/enhancer regions. They are useful when studying gene function in adult epithelium of the distal intestinal tract.

Detailed description

Mice hemizygous for the CDX2P-CreERT2 transgene are viable and fertile, with a 9.5 kb human caudal type homeo box 2 (CDX2) promoter/enhancer sequence directing expression of CreER^T2 fusion gene (a Cre recombinase fused to a human estrogen receptor ligand binding domain). Restricted to the cytoplasm, Cre-ER^T2 can only gain access to the nuclear compartment after exposure to tamoxifen. When these mice are bred with mice containing loxP-flanked sequence, tamoxifen-inducible, Cre-mediated recombination will result in deletion of the floxed sequences in the Cre-expressing cells of the offspring. Specifically, mosaic Cre recombinase expression is observed epithelium from the distal ileum and cecum, and throughout the colon from the crypt base to the luminal surface. These mice permit the study of gene defects in adult epithelium as compared with B6.Cg-Tg(CDX2-cre)101Erf/J mice (Stock No. 009350) and B6.Cg-Tg(CDX2-cre*)189Erf/J mice (Stock No. 009352), both expressing cre in developing caudal tissues. These strains prove problematic for targeting some genes, such as those required for early development of the caudal region of the embryo.

When bred to mice expressing a conditional Apc (adenomatosis polyposis coli) allele, tamoxifen-inducible, Cre-recombination in the offspring results in inactivation of Apc in epithelium in the distal ileum, cecum, and colon. This Apc deficiency leads to increased beta-catenin levels, activation of the expression of beta-catenin/TCF (T cell factor) regulated genes, initiation of crypt budding, and morphological changes indicative of adenomatous lesion development in the regions of the intestinal tract where APC was inactivated.

The donating investigator of the CDX2-Cre-ER^T2 transgene reports that cre expression is leaky in 10% of mice. It is the experience of The Jackson Laboratory that cre expression is leaky in approximately 30% of untreated mice as determined by the presence of malignant tumors of the hair follicle in Stock No. 035169 (November 2021).

Development

The CDX2P-CreERT2 transgene was designed with a 9.5 kb promoter fragment from the 5' flanking sequences of human caudal type homeo box 2 (CDX2) gene, a creER^T2 fusion gene (a Cre recombinase fused to a human estrogen receptor ligand binding domain), and a bovine growth hormone polyadenylation cassette. This transgene was injected into (C57BL/6J x SJL/J) hybrid cells. Transgenic mice from founder line 752 were bred to C57BL/6J mice. The donating investigator reports that this strain was maintained by breeding hemizygous mice with C57BL/6J inbred mice for at least 4 generations. Upon arrival at The Jackson Laboratory, CDX2P9.5-NLSCre transgenic mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

Allele

Symbol: Tg(CDX2-cre/ERT2)752Erf
Name: transgene insertion 752, Eric Fearon
MGI accession ID: MGI:5477802
Generation method: Transgenic
Attributes: Recombinase-expressing; Inducible
Marker symbol: Tg(CDX2-cre/ERT2)752Erf
Marker name: transgene insertion 752, Eric Fearon
Chromosome: UN
Strain of origin: (C57BL/6J x SJL/J)
Expressed genes: cre/ERT2,Cre recombinase and estrogen receptor 1 (human) fusion gene,
Site of expression: Upon tamoxifen administration, cre activity was detected in the distal ileal, cecal, colonic, and rectal epithelium.
Molecular note: The transgene was designed with a 9.5 kb promoter fragment from the 5' flanking sequences of human caudal type homeo box 2 (CDX2) gene, a creERT2 fusion gene (a Cre recombinase fused to a human estrogen receptor ligand binding domain), and a bovine growth hormone polyadenylation cassette. This transgene was injected into (C57BL/6J x SJL/J) hybrid cells. Transgenic mice from founder line 752 were bred to C57BL/6J mice. The donating investigator reports that this strain was maintained by breeding hemizygous mice with C57BL/6J inbred mice for at least 4 generations.