The Wt1CreERT2 knock-in allele in these mice both abolishes Wilms tumor 1 homolog gene function and directs expression of the CreERT2 fusion protein to proepicardium and epicardium by the Wt1 promoter/enhancer elements. As Wt1 is expressed in the developing genitourinary system and in the mesothelia overlying most visceral organs, these mutant mice are useful as a tamoxifen-inducible Cre-lox tool for lineage-tracing/marking Wt1-expressing cells for studying cardiomyocytes in the developing heart.
William T Pu, Children's Hospital Boston, Harvard MS
Genetic Background | Generation |
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?+pN1F5
|
Allele Type | Gene Symbol | Gene Name |
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Targeted (Recombinase-expressing, Inducible) | Wt1 | Wilms tumor 1 homolog |
Starting at:
$278.00 Domestic price for female 4-week |
356.51 Domestic price for breeder pair |
Homozygous mice die between embryonic day (E)13.5 and birth with defects of heart, kidney, gonads, and multiple other organs. Heterozygous (Wt1CreERT2/+) mice are viable and fertile. The Wt1CreERT2 "knock-in" allele both abolishes Wt1 gene function and has expression of the CreERT2 fusion protein (CreERT2) under control of the Wt1 promoter/enhancer elements. In heart from heterozygous mice, CreERT2 expression is directed to proepicardium and epicardium from E9.5 to E15.5, and is not found in the myocardium. CreERT2 fusion gene activity is inducible; observed following tamoxifen administration. As such, when Wt1CreERT2 mice are bred with mice containing loxP-flanked sequence, tamoxifen-inducible Cre-mediated recombination will result in deletion of the floxed sequences in the Wt1-expressing cells of the offspring. The donating investigator reports that Cre activity may be observed prior to tamoxifen exposure only in epicardium of adult mice following myocardial infarction. As Wt1 is expressed in the developing genitourinary system and in the mesothelia overlying most visceral organs, these mutant mice are useful as a tamoxifen-inducible Cre-lox tool for lineage-tracing/marking Wt1-expressing cells for studying cardiomyocytes in the developing heart.
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.
A targeting vector was designed to replace exon 1 of the Wt1 (Wilms tumor 1 homolog) locus with a CreERT2 fusion gene (Cre-ERT2; Cre recombinase fused to a G400V/M543A/L544A triple mutation of the human estrogen receptor ligand binding domain), an SV40 polyA signal, and an frt-flanked pgk-Neo cassette. The donating investigator reports that this construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts and chimeric mice were bred with outbred Swiss Webster (CFW) mice to originate the colony. To remove the pgk-Neo cassette, mutant mice were bred with Actin-FLPe mice (mostly C57BL/6 genetic background; see Stock No. 005703). The resulting Wt1CreERT2 mice were subsequently mated with outbred Swiss Webster (CFW) mice for several generations (and the FLPe transgene was removed) prior to sending to The Jackson Laboratory Repository. Upon arrival, mice were bred with B6129SF1/J hybrid mice (Stock No. 101043) for at least one generation to establish the Wt1CreERT2 colony.
Expressed Gene | cre/ERT2, Cre recombinase and estrogen receptor 1 (human) fusion gene, |
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Site of Expression | Cre activity is observed prior to tamoxifen exposure only in epicardium of adult mice following myocardial infarction. |
Allele Name | targeted mutation 2, William T Pu |
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Allele Type | Targeted (Recombinase-expressing, Inducible) |
Allele Synonym(s) | Wt1CreERT2; Wt1iCre; Wt1tm2(cre/ESR1)Wtp |
Gene Symbol and Name | Wt1, Wilms tumor 1 homolog |
Gene Synonym(s) | |
Expressed Gene | cre/ERT2, Cre recombinase and estrogen receptor 1 (human) fusion gene, |
Site of Expression | Cre activity is observed prior to tamoxifen exposure only in epicardium of adult mice following myocardial infarction. |
Strain of Origin | 129S4/SvJae |
Chromosome | 2 |
Molecular Note | Exon 1 was replaced with an inducible cre ESR1 (ERT2) fusion followed by an frt-flanked neo cassette. Germ line, flp-mediated recombination was used to remove the neo cassette. |
Mutations Made By | William Pu, Children's Hospital Boston, Harvard MS |
When maintaining a live colony, heterozygous mice may be bred together or to wildtype siblings. Homozygous mice die before birth.
When using the Wt1CreERT2 mouse strain in a publication, please cite the originating article(s) and include JAX stock #010912 in your Materials and Methods section.
Service/Product | Description | Price |
---|---|---|
Heterozygous or wildytpe for Wt1<tm2(cre/ERT2)Wtp> |
Frozen Mouse Embryo | STOCK Wt1<tm2(cre/ERT2)Wtp>/J | $2595.00 |
Frozen Mouse Embryo | STOCK Wt1<tm2(cre/ERT2)Wtp>/J | $2595.00 |
Frozen Mouse Embryo | STOCK Wt1<tm2(cre/ERT2)Wtp>/J | $3373.50 |
Frozen Mouse Embryo | STOCK Wt1<tm2(cre/ERT2)Wtp>/J | $3373.50 |
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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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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