FVB.Cg-Tg(CAG-cre/Esr1*)5Amc/J

Stock number: 017595
Product name: CAGGCre-ER^TM
Research areas: Cancer Research, Neurobiology Research, Research Tools

Description

These CAGGCre-ER^TM transgenic mice have widespread expression of a tamoxifen-inducible Cre recombinase.

Detailed description

These CAGGCre-ER^TM transgenic mice have a tamoxifen-inducible cre-mediated recombination system driven by the chicken beta actin promoter/enhancer coupled with the cytomegalovirus (CMV) immediate-early enhancer. When bred with mice containing loxP-flanked sequences, tamoxifen-inducible Cre-mediated recombination results in deletion of the floxed sequences in widespread cells/tissues of the offspring. Tamoxifen administration will also induce Cre recombination in developing embryos of treated mothers and in cultured cells derived from transgenic mice. Homozygous mice are not viable or fertile. Heterozygous mutant mice are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities.

The CreERTM fusion protein consists of Cre recombinase fused to a G525R mutant form of the mouse estrogen receptor; which does not bind its natural ligand (17β-estradiol) at physiological concentrations but will bind the synthetic estrogen receptor ligands 4-hydroxytamoxifen (OHT or tamoxifen) and, with lesser sensitivity, ICI 182780. Restricted to the cytoplasm, Cre-ERT can only gain access to the nuclear compartment after exposure to tamoxifen. To counteract the mixed estrogen agonist effects of tamoxifen injections, which can result in late fetal abortions in pregnant mice, progesterone may be coadministered.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for these FVB/N-congenic CAGGCre-ER^TM mice. It should be noted that the phenotype of these mice could vary from that originally described. We may modify the FVB/N-congenic CAGGCre-ER^TM strain description if necessary as published results become available.

Development

The pCAGGCre-ER^TM transgene was designed by Drs. Shigemi Hayashi and Andrew P. McMahon (while at Harvard University) to have the CMV-IE enhancer/chicken β-actin/rabbit β-globin hybrid promoter (CAG; originally from the pCAGGS vector) and CreERTM fusion gene (CreER^TM; Cre recombinase fused to a G525R mutant form of the mouse estrogen receptor ligand binding domain). The transgene was introduced into B6CBF1 donor eggs. The resulting transgenic males were backcrossed for two generations on the SWR background. In 2002, transgenic mice were sent to The Jackson Laboratory Repository (as Stock No. 004453). In 2003, some of the transgenic mice were backcrossed to C57BL/6J inbred mice (Stock No. 000664) for at least five generations to generate a C57BL/6J-congenic line (Stock No. 004682). In 2012, some of the C57BL/6J-congenic mice were subsequently backcrossed to FVB/NJ inbred mice (Stock No. 001800) for several generations using a marker-assisted, speed congenic approach to generate this FVB/NJ-congenic strain (Stock No. 017595).

In 2022, the Tg(CAG-cre/Esr1*)5Amc transgene creator's laboratory provided the cDNA sequence of the Cre‐ERTM portion - available here. Currently, this transgene is present in the following available Stock Nos. 004682, 004453, 008783, 008813, 017595, 019102, 034795, 034859.

Allele

Symbol: Tg(CAG-cre/Esr1*)5Amc
Name: transgene insertion 5, Andrew P McMahon
MGI accession ID: MGI:2182767
Generation method: Transgenic
Attributes: Recombinase-expressing; Inducible
Synonyms: CAG-CreEr; CAGG-Cre; CaggCreER; CAGGCre-ER; CAGGCre-ER^TM; CAGGCre-ERtm line 5.8; CAGGS-CreER; CAGGS-CreErT; CMV-creERT; Cre-ER; Cre-ER^TM; CreESR^T; ER-cre; Tg(CAG-cre/Esr1)5Amc; Tg(cre/Esr1)5Amc; Tg:Cag-Cre/Esr1; Tg^CreER; TgCAGGCreER; uCreER^T; CAG-Cre
Marker symbol: Tg(CAG-cre/Esr1*)5Amc
Marker name: transgene insertion 5, Andrew P McMahon
Marker synonyms: CAG-CreERT2; CAGGCre-ER; CAGGCre-ER^TM; CAGG-CreERT2; CAGGCre-ERtm line 5.8; CAGGS-CreER; CAGGS-CreErT; CMV-creERT; Cre-ER; Cre-ERTM; ER-cre; Tg(CAG-cre/Esr1)5Amc; Tg(cre/Esr1)5Amc
Chromosome: UN
Strain of origin: (C57BL/6 x CBA)F1
Expressed genes: cre/Esr1,Cre recombinase and estrogen receptor 1 fusion gene,
Site of expression: tamoxifen-inducible cre; widespread pattern of expression; tamoxifen administration will also induce Cre recombination in developing embryos of treated mothers and in cultured cells derived from transgenic mice
Molecular note: This transgene expresses a fusion protein consisting of Cre recombinase joined to the ligand-binding domain of a mouse estrogen receptor modified to bind to 4-hydroxytamoxifen, but not to endogenous estrogen. The CAG promoter, containing a chicken beta actin promoter/enhancer coupled with the cytomegalovirus immediate-early (CMV-IE) enhancer, drives high levels of expression in most tissues. In the presence of tamoxifen, the fusion protein is transported into the nucleus, where cre can excise loxP-flanked segments from conditionally modified genes.
General note: Homozygous transgenic mice are not viable or fertile. Hemizygous transgenic mice are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities.

In transgenic mice the mutant mouse estrogen receptor does not bind natural ligand at physiological concentrations but will bind the synthetic ligand, 4-hydroxytamoxifen. Restricted to the cytoplasm, the Cre/Esr1 fusion protein can only gain access to the nuclear compartment after exposure to tamoxifen. When crossed with a strain containing loxP sites flanking a sequence of interest, tamoxifen induced, Cre-mediated targeted deletions are generated in the offspring. Tamoxifen administration will induce Cre recombination in developing embryos of treated mothers and in cultured cells derived from transgenic mice.

Note that this transgene does not contain the cre/ERT2 fusion but was mistakenly referred to by the synonym CAG-CreERT2 in publication. J:136965

Note that this transgene does not contain the cre/ERT2 fusion but was mistakenly referred to by the synonym CAGG-CreERT2 in publication. J:130851