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.

Expression Data

Expressed Gene	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.

Control Suggestions

Noncarrier

Additional Information

Considerations for Choosing Controls

Selected References

Riccomagno MM; Takada S; Epstein DJ. 2005. Wnt-dependent regulation of inner ear morphogenesis is balanced by the opposing and supporting roles of Shh. Genes Dev 19(13):1612-23. PubMed: 15961523 MGI: J:99408

View All References

Genetics

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

Allele Symbol: Tg(TCF/Lef1-cre/ERT2)1Dje

Allele Name	transgene insertion 1, Douglas J Epstein
Allele Type	Transgenic (Inducible, Recombinase-expressing)
Allele Synonym(s)	Tg(Fos-cre/ERT2)1Dje; TopCreERT2
Gene Symbol and Name	Tg(TCF/Lef1-cre/ERT2)1Dje, transgene insertion 1, Douglas J Epstein
Gene Synonym(s)	Tg(Fos-cre-ERT2)1Dje; Tg(Fos-cre/ERT2)1Dje; TopCreERT2
Promoter	Fos, FBJ osteosarcoma oncogene, mouse, laboratory
Promoter	Lef1, lymphoid enhancer binding factor 1, mouse, laboratory
Expressed Gene	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.
Strain of Origin	Not Specified
Chromosome	UN
Molecular Note	Three consensus LEF/TCF-binding motifs upstream of a minimal Fos promoter were used to drive expression of a tamoxifen inducible cre construct.
Mutations Made By	Douglas Epstein, University of Pennsylvania

Disease/Phenotype

Disease Terms

Research Areas By Genotype

This mouse can be used to support research in many areas including:

Developmental Biology Research
- Neural Tube Defects
Research Tools
- Cre-lox System
  - Cre Recombinase Expression: Inducible

Genotype: cre related

Research Tools
- Cre-lox System
- Genetics Research
  - Mutagenesis and Transgenesis
  - Mutagenesis and Transgenesis: Cre-lox System

References

Riccomagno MM; Takada S; Epstein DJ. 2005. Wnt-dependent regulation of inner ear morphogenesis is balanced by the opposing and supporting roles of Shh. Genes Dev 19(13):1612-23. PubMed: 15961523 MGI: J:99408

Additional - Tg(TCF/Lef1-cre/ERT2)1Dje related

Brown AS; Rakowiecki SM; Li JY; Epstein DJ. 2015. The cochlear sensory epithelium derives from Wnt responsive cells in the dorsomedial otic cup. Dev Biol 399(1):177-87. PubMed: 25592224 MGI: J:219804
Rakowiecki S; Epstein DJ. 2013. Divergent roles for Wnt/beta-catenin signaling in epithelial maintenance and breakdown during semicircular canal formation. Development 140(8):1730-9. PubMed: 23487315 MGI: J:195122

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service	Genotype	Price
	Hemizygous or Non carrier for Tg(TCF/Lef1-cre/ERT2)1Dje

Progeny testing is not required

The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks.

The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.

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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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