B6;129-Gt(ROSA)26Sor^{tm1(cre/ERT)Nat}/J

Stock number: 004847
Product name: R26CreER
Research areas: Developmental Biology Research, Internal/Organ Research, Reproductive Biology Research, Research Tools

Description

These R26CreER mutant mice have a tamoxifen-inducible Cre-mediated recombination system driven by the endogenous mouse Gt(ROSA)26Sor promoter. When crossed with a strain containing a loxP site-flanked sequence of interest, this mutant is useful for generating tamoxifen-induced, Cre-mediated targeted deletions.

Of note, a similar strain (Stock No. 008463 B6.129-Gt(ROSA)26Sor^{tm1(cre/ERT2)Tyj}/J) enables temporal control of floxed gene expression in vivo and is reportedly more sensitive to tamoxifen than Stock No. 004847.

Detailed description

These R26CreER mutant mice have a tamoxifen-inducible Cre-mediated recombination system driven by the endogenous mouse Gt(ROSA)26Sor promoter. The mutant allele consists of a fusion product involving Cre recombinase and an altered version of the mouse estrogen receptor ligand binding domain. The mutant ligand binding domain does not bind natural ligand at physiological concentrations but will bind the synthetic ligand, 4-hydroxytamoxifen. Restricted to the cytoplasm, the CRE/ESR1 protein can only gain access to the nuclear compartment to mediate recombination after exposure to tamoxifen. Tamoxifen administration will also induce Cre recombination in the developing embryos of treated mothers. When crossed with a strain containing a loxP site-flanked sequence of interest, this mutant is useful for generating tamoxifen-induced, Cre-mediated targeted deletions. Homozygous mutant mice are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities.

Development

A targeting vector containing a PGK-neo cassette and Cre recombinase/estrogen receptor ligand-binding domain fusion protein sequence was used to insert the fusion protein into a site located within intron 1 of the GT(ROSA)26Sor locus. The construct was introduced into 129X1/SvJ x 129S1/Sv-derived R1-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. Correctly targeted ES cells were injected into C57BL/6J blastocysts to obtain chimeric animals.

Allele

Symbol: Gt(ROSA)26Sor^{tm1(cre/ERT)Nat}
Name: targeted mutation 1, Jeremy Nathans
MGI accession ID: MGI:2669525
Generation method: Targeted
Attributes: Recombinase-expressing; Inducible
Marker symbol: Gt(ROSA)26Sor
Marker name: gene trap ROSA 26, Philippe Soriano
Chromosome: 6
Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl⁺
Expressed genes: cre/ER,cre inducible estrogen receptor,bacteriophage P1/Human
Site of expression: tamoxifen-inducible cre; when crossed with a strain containing a loxP site-flanked sequence of interest, this mutant is useful for generating tamoxifen-induced, Cre-mediated targeted deletions
Molecular note: A cDNA fragment encoding a fusion protein comprised of cre recombinase and the ligand binding domain of Esr1 was inserted at the endogenous locus via homologous recombination. The initiator methionine was placed in an optimal translational context, allowing for near ubiquitous expression via the endogenous promoter. Activation of cre recombinase activity is dependent on the administration of 4-HO-tamoxifen.