Overview

Also Known As: Wt1^CreERT2

The Wt1^CreERT2 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.

Donating Investigator

William T Pu, Children's Hospital Boston, Harvard MS

Genetic overview

Genetic Background	Generation
	?+pN1 (2017-11-16 00:00:00)

Wt1^{tm2(cre/ERT2)Wtp}

Allele Type	Gene Symbol	Gene Name
Targeted (Recombinase-expressing, Inducible)	Wt1	Wilms tumor 1 homolog

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Research Applications

Developmental Biology Research
Research Tools
Cardiovascular Research
Internal/Organ Research
Reproductive Biology Research

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Base Price

Starting at:

$76.22 Domestic price for female

347.22 Domestic price for breeder pair

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Details

Detailed Description

Homozygous mice die between embryonic day (E)13.5 and birth with defects of heart, kidney, gonads, and multiple other organs. Heterozygous (Wt1^CreERT2/+) mice are viable and fertile. The Wt1^CreERT2 "knock-in" allele both abolishes Wt1 gene function and has expression of the CreER^T2 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 Wt1^CreERT2 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.

Development

A targeting vector was designed to replace exon 1 of the Wt1 (Wilms tumor 1 homolog) locus with 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), 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 Wt1^CreERT2 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 Wt1^CreERT2 colony.

Expression Data

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.

Control Suggestions

Wild-type from the colony ()

Additional Information

Considerations for Choosing Controls

Selected References

Zhou B; Ma Q; Rajagopal S; Wu SM; Domian I; Rivera-Feliciano J; Jiang D; von Gise A; Ikeda S; Chien KR; Pu WT. 2008. Epicardial progenitors contribute to the cardiomyocyte lineage in the developing heart. Nature 454(7200):109-13PubMed: 18568026 MGI: J:137426

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Genetics

Wt1^{tm2(cre/ERT2)Wtp}

Allele Symbol: Wt1^{tm2(cre/ERT2)Wtp}

Allele Name	targeted mutation 2, William T Pu
Allele Type	Targeted (Recombinase-expressing, Inducible)
Allele Synonym(s)	Wt1^{tm2(cre/ERT2)Wtp}; targeted mutation 2, William T Pu
Gene Symbol and Name	Wt1, Wilms tumor 1 homolog
Gene Synonym(s)	Wt-1; NPHS4; D630046I19Rik; GUD; Wt-1; WT33; WAGR; AWT1; WIT-2; RIKEN cDNA D630046I19 gene; D630046I19Rik
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

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Developmental Biology Research
- Internal/Organ Defects
  - gonads
  - kidneys, gonads, heart
  - heart
  - kidney
- Embryonic Lethality (Homozygous)
Research Tools
- Genetics Research
  - Tissue/Cell Markers: Cre-lox System
  - Mutagenesis and Transgenesis
  - Tissue/Cell Markers
  - Mutagenesis and Transgenesis: Cre-lox System
- Cre-lox System
  - Cre Recombinase Expression: Inducible
  - Cre Recombinase Expression
- Cardiovascular Research
  - Cre-lox System
- Developmental Biology Research
  - Cre-lox System
Cardiovascular Research
- Heart Abnormalities
Internal/Organ Research
- Heart Abnormalities
- Kidney Defects
Reproductive Biology Research
- Developmental Defects Affecting Gonads

Mammalian Phenotype Terms by Genotype

References

Zhou B; Ma Q; Rajagopal S; Wu SM; Domian I; Rivera-Feliciano J; Jiang D; von Gise A; Ikeda S; Chien KR; Pu WT. 2008. Epicardial progenitors contribute to the cardiomyocyte lineage in the developing heart. Nature 454(7200):109-13PubMed: 18568026 MGI: J:137426

Additional - Wt1^{tm2(cre/ERT2)Wtp} related

Technical Support

Contact Technical Support

Genotyping Protocols
- QPCR: Wt1^{tm2(cre/ERT2)Wtp}qPCR
- Genotyping resources and troubleshooting
Dietary Information
- LabDiet® 5K52 formulation (6% fat)
Breeding Considerations

When maintaining a live colony, heterozygous mice may be bred together or to wildtype siblings. Homozygous mice die before birth.
- Additional Breeding and Husbandry Support
Mating System
- Heterozygote x +/+ sibling
Citation
When using the Wt1^CreERT2 mouse strain in a publication, please cite the originating article(s) and include JAX stock #010912 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

AX10 (Standard)

Pricing & Availability

Repository Live

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Breeder Pair

Sex

Genotype

Price

Female
Male

Cryorecovery - Pricing

Service	Genotype	Price
	Heterozygous or wildytpe for Wt1<tm2(cre/ERT2)Wtp>

We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We 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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Also Known As: Wt1CreERT2

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Wt1tm2(cre/ERT2)Wtp

Allele Symbol: Wt1tm2(cre/ERT2)Wtp

Disease Terms

Research Areas By Genotype

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

Mammalian Phenotype Terms by Genotype

References

Additional - Wt1tm2(cre/ERT2)Wtp related

Genotyping Protocols

Dietary Information

Breeding Considerations

Mating System

Citation

Animal Health Reports

Live Mouse

Breeder Pair

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Also Known As: Wt1^CreERT2

Wt1^{tm2(cre/ERT2)Wtp}

Allele Symbol: Wt1^{tm2(cre/ERT2)Wtp}

Additional - Wt1^{tm2(cre/ERT2)Wtp} related