STOCK Tg(TCF/Lef1-cre/ERT2)1Dje/J

Stock number: 016236
Research areas: Developmental Biology Research, Research Tools

Description

TopCreERT2 transgenic mice express a CreER^T2 fusion protein under the control of three copies of a T cell specific transcription factor/lymphoid enhancer-binding factor 1 (TCF/Lef1) response element and a c-fos minimal promoter. This strain may useful for studying the Wnt signaling pathway.

Detailed description

TopCreERT2 transgenic mice express a CreER^T2 fusion protein under the control of three copies of a T cell specific transcription factor/lymphoid enhancer-binding factor 1 (TCF/Lef1) response element and a c-fos minimal promoter. Mice hemizygous for the transgene are viable, fertile, and normal in size. Wnt (wingless-related MMTV) family members are required for triggering embryonic axis formation and for proper development. Wnt signaling results in phosphorylation and nuclear localization of β-catenin, a transcriptional co-activator protein, which, together with the TCF/Lef family of transcription factors, induces the transcription of downstream genes. TopCreERT2 transgenic mice contain three copies of nuclear localized TCF/Lef1 DNA binding sites, which provides increased sensitivity to Wnt/β-catenin signaling. Cre-ERT2 fusion gene activity is inducible; observed at high levels following tamoxifen administration. When TopCreERT2 transgenic mice are bred with mice containing loxP-flanked sequences, tamoxifen-inducible Cre-mediated recombination will result in deletion of the floxed sequences in cells of the double mutant offspring with active Wnt-signaling. Specifically, the TopCreERT2 transgene directs cre expression in the dorsal regions of the otic vesicle of the inner ear. This strain may useful for studying the Wnt signaling pathway.

The Cre-ERT2 fusion protein consists of Cre recombinase fused to a triple mutant form of the human 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-ERT2 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.

Development

The TopCreERT2 transgene was designed with three copies of a T cell specific transcription factor/lymphoid enhancer-binding factor 1 (TCF/Lef1) DNA binding site and a minimal c-fos promoter driving expression of a CreER^T2 fusion gene (Cre-ER^T2; Cre recombinase fused to a G400V/M543A/L544A triple mutation of the human estrogen receptor ligand binding domain). The transgene was microinjected into fertilized (B6J x SJL)F1 oocytes, and founder mice were bred to outbred CD1 mice to establish a colony. Upon arrival at The Jackson Laboratory, transgenic mice were bred to C57BL/6J inbred mice (Stock No. 000664) to establish the colony.

Allele

Symbol: Tg(TCF/Lef1-cre/ERT2)1Dje
Name: transgene insertion 1, Douglas J Epstein
MGI accession ID: MGI:3836892
Generation method: Transgenic
Attributes: Recombinase-expressing; Inducible
Marker symbol: Tg(TCF/Lef1-cre/ERT2)1Dje
Marker name: transgene insertion 1, Douglas J Epstein
Chromosome: UN
Strain of origin: Not Specified
Expressed genes: cre,cre recombinase,bacteriophage P1
Site of expression: This transgene directs cre expression in the dorsal regions of the otic vesicle of the inner ear.
Molecular note: Three consensus LEF/TCF-binding motifs upstream of a minimal Fos promoter were used to drive the expression of a tamoxifen-inducible cre construct.