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| 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. | |||||||||||||||||||
- Description
- Disease & phenotype
- Genes & alleles
- Genotyping
- Health & care
- References
- Pricing & purchasing
- Terms of use
Description
Strain Information
Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Heterozygote x +/+ sibling (Female x Male) 23-MAR-10 Species laboratory mouse Generation F?+F1 (03-SEP-10)
Generation DefinitionsDonating Investigator William T Pu, Children's Hospital Boston, Harvard MS Description
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.
Development
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.
Control Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying other alleles of Wt1
002719 B6.129S4-Wt1tm1Jae/J 002332 B6;129S4-Wt1tm1Jae/J 006817 D2.129S4(Cg)-Wt1tm1Jae/EiJ 010911 STOCK Wt1tm1(EGFP/cre)Wtp/J View Strains carrying other alleles of Wt1 (4 strains)
Additional Web Information
Introduction to Cre-lox technology
Phenotype
Phenotype Information
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Aniridia; AN (WT1)
Denys-Drash Syndrome; DDS (WT1)
Frasier Syndrome (WT1)
Meacham Syndrome (WT1)
Mesothelioma, Malignant; MESOM (WT1)
Nephrotic Syndrome, Type 4; NPHS4 (WT1)
Wilms Tumor 1; WT1 (WT1)
Wilms Tumor, Aniridia, Genitourinary Anomalies, and Mental Retardation Syndrome; WAGR (WT1)
This mouse can be used to support research in many areas including:
cre relatedCardiovascular Research
Heart Abnormalities
Developmental Biology Research
Embryonic Lethality (Homozygous)
Internal/Organ Defects
gonads
heart
kidney
kidneys, gonads, heart
Internal/Organ Research
Heart Abnormalities
Kidney Defects
Reproductive Biology Research
Developmental Defects Affecting Gonads
Research Tools
Cardiovascular Research
Cre-lox System
Cre-lox System
Cre Recombinase Expression
Cre Recombinase Expression: Inducible
Developmental Biology Research
Cre-lox System
Genetics Research
Mutagenesis and Transgenesis
Mutagenesis and Transgenesis: Cre-lox System
Tissue/Cell Markers
Tissue/Cell Markers: Cre-lox System
Research Tools
Cre-lox System
Genetics Research
Mutagenesis and Transgenesis
Mutagenesis and Transgenesis: Cre-lox System
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Wt1tm2(cre/ERT2)Wtp | ||
|---|---|---|---|
| Allele Name | targeted mutation 2, William T Pu | ||
| Allele Type | Targeted (knock-in) | ||
| Common Name(s) | Wt1CreERT2; Wt1iCre (i represents inducible); Wt1tm2(cre/ESR1)Wtp; | ||
| Mutation Made By | William Pu, Children's Hospital Boston, Harvard MS | ||
| Strain of Origin | 129S4/SvJae | ||
| Site of Expression | Cre activity is observed prior to tamoxifen exposure only in epicardium of adult mice following myocardial infarction. | ||
| Expressed Gene | cre, cre recombinase, bacteriophage P1 | ||
| Cre recombinase is an enzyme derived from the bacteriophage P1 that specifically recognizes loxP sites. Cre has been shown to effectively mediate the excision of DNA located between loxP sites. After the excision event, the DNA ends recombine leaving a single loxP site in place of the intervening sequence. | |||
| Driver Note | Wt1 | ||
| Inducible Note | induced by tamoxifen | ||
| 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. [MGI Ref ID J:137426] | ||
| Gene Symbol and Name | Wt1, Wilms tumor 1 homolog | ||
| Chromosome | 2 | ||
| Gene Common Name(s) | AWT1; D630046I19Rik; EWS-WT1; GUD; NPHS4; RIKEN cDNA D630046I19 gene; WAGR; WIT-2; WT33; Wt-1; | ||
Genotyping
Genotyping Information
Genotyping Protocols
Wt1tm2(cre/ERT2)Wtp, Standard PCR
Wt1tm2(cre/ERT2)WtpqPCR, QPCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Selected Reference(s)
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):109-13. [PubMed: 18568026] [MGI Ref ID J:137426]
Additional References
Wt1tm2(cre/ERT2)Wtp relatedAsahina K; Zhou B; Pu WT; Tsukamoto H. 2011. Septum transversum-derived mesothelium gives rise to hepatic stellate cells and perivascular mesenchymal cells in developing mouse liver. Hepatology 53(3):983-95. [PubMed: 21294146] [MGI Ref ID J:170930]
Baek ST; Tallquist MD. 2012. Nf1 limits epicardial derivative expansion by regulating epithelial to mesenchymal transition and proliferation. Development 139(11):2040-9. [PubMed: 22535408] [MGI Ref ID J:183991]
Barnes RM; Firulli BA; Vandusen NJ; Morikawa Y; Conway SJ; Cserjesi P; Vincentz JW; Firulli AB. 2011. Hand2 Loss-of-Function in Hand1-Expressing Cells Reveals Distinct Roles in Epicardial and Coronary Vessel Development. Circ Res 108(8):940-9. [PubMed: 21350214] [MGI Ref ID J:171088]
Greif DM; Kumar M; Lighthouse JK; Hum J; An A; Ding L; Red-Horse K; Espinoza FH; Olson L; Offermanns S; Krasnow MA. 2012. Radial construction of an arterial wall. Dev Cell 23(3):482-93. [PubMed: 22975322] [MGI Ref ID J:189012]
Li Y; Wang J; Asahina K. 2013. Mesothelial cells give rise to hepatic stellate cells and myofibroblasts via mesothelial-mesenchymal transition in liver injury. Proc Natl Acad Sci U S A 110(6):2324-9. [PubMed: 23345421] [MGI Ref ID J:194339]
Manuylov NL; Zhou B; Ma Q; Fox SC; Pu WT; Tevosian SG. 2011. Conditional ablation of Gata4 and Fog2 genes in mice reveals their distinct roles in mammalian sexual differentiation. Dev Biol 353(2):229-41. [PubMed: 21385577] [MGI Ref ID J:173838]
Miyoshi H; Ajima R; Luo CT; Yamaguchi TP; Stappenbeck TS. 2012. Wnt5a potentiates TGF-beta signaling to promote colonic crypt regeneration after tissue injury. Science 338(6103):108-13. [PubMed: 22956684] [MGI Ref ID J:187747]
Smith CL; Baek ST; Sung CY; Tallquist MD. 2011. Epicardial-derived cell epithelial-to-mesenchymal transition and fate specification require PDGF receptor signaling. Circ Res 108(12):e15-26. [PubMed: 21512159] [MGI Ref ID J:185693]
Zhou B; von Gise A; Ma Q; Hu YW; Pu WT. 2010. Genetic fate mapping demonstrates contribution of epicardium-derived cells to the annulus fibrosis of the mammalian heart. Dev Biol 338(2):251-61. [PubMed: 20025864] [MGI Ref ID J:156703]
von Gise A; Zhou B; Honor LB; Ma Q; Petryk A; Pu WT. 2011. WT1 regulates epicardial epithelial to mesenchymal transition through beta-catenin and retinoic acid signaling pathways. Dev Biol 356(2):421-31. [PubMed: 21663736] [MGI Ref ID J:175466]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX11
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, heterozygous mice may be bred together or to wildtype siblings. Homozygous mice die before birth. Mating System Heterozygote x +/+ sibling (Female x Male) 23-MAR-10 Diet Information LabDiet® 5K52/5K67
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
|
Live Mice
Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $232.00 Female or Male Heterozygous for Wt1tm2(cre/ERT2)Wtp
Price per Pair (US dollars $) Pair Genotype $302.00 Heterozygous for Wt1tm2(cre/ERT2)Wtp x Wild-type for Wt1tm2(cre/ERT2)Wtp $302.00 Wild-type for Wt1tm2(cre/ERT2)Wtp x Heterozygous for Wt1tm2(cre/ERT2)Wtp Standard Supply
Repository-Live.
Repository-Live represents an exclusive set of over 1500 unique mouse models across a vast array of research areas. Breeding colonies provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. If a Repository strain is not immediately available, then within 2 to 3 business days, you will receive an estimated availability timeframe for your inquiry or order along with various delivery options. Repository strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping. We will note and try to accommodate requests for specific ages of Repository strains but cannot guarantee provision of these strains at specific ages. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, please let us know.
| Pricing for International shipping destinations |
|
Live Mice
Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $301.60 Female or Male Heterozygous for Wt1tm2(cre/ERT2)Wtp
Price per Pair (US dollars $) Pair Genotype $392.60 Heterozygous for Wt1tm2(cre/ERT2)Wtp x Wild-type for Wt1tm2(cre/ERT2)Wtp $392.60 Wild-type for Wt1tm2(cre/ERT2)Wtp x Heterozygous for Wt1tm2(cre/ERT2)Wtp Standard Supply
Repository-Live.
Repository-Live represents an exclusive set of over 1500 unique mouse models across a vast array of research areas. Breeding colonies provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. If a Repository strain is not immediately available, then within 2 to 3 business days, you will receive an estimated availability timeframe for your inquiry or order along with various delivery options. Repository strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping. We will note and try to accommodate requests for specific ages of Repository strains but cannot guarantee provision of these strains at specific ages. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, please let us know.
|
|
|
Standard Supply
Repository-Live.
Repository-Live represents an exclusive set of over 1500 unique mouse models across a vast array of research areas. Breeding colonies provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. If a Repository strain is not immediately available, then within 2 to 3 business days, you will receive an estimated availability timeframe for your inquiry or order along with various delivery options. Repository strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping. We will note and try to accommodate requests for specific ages of Repository strains but cannot guarantee provision of these strains at specific ages. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, please let us know.
Control Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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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.Ordering Information
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