Overview

Also Known As:Wt1^flox

The Wt1^flox allele has loxP sites flanking exons 8-9 of the Wilms tumor 1 homolog gene. Removal of the floxed sequence creates a null allele. These mice may be useful for generating tissue-specific WT1-deletion for studying the role of this zinc finger nuclear transcription factor in leukemias and solid tumors.

Donating Investigator

Vicki Huff, University of Texas, M. D. Anderson Cancer Center

Genetic overview

Genetic Background	Generation

Wt1^tm2Vih

Allele Type	Gene Symbol	Gene Name
Targeted (Conditional ready (e.g. floxed), No functional change)	Wt1	Wilms tumor 1 homolog

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Research Applications

Cancer Research
Cell Biology Research
Developmental Biology Research
Research Tools
Endocrine Deficiency Research
Internal/Organ Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

The Wilms' tumor (WT) suppressor gene (Wt1) encodes a zinc finger nuclear transcription factor. WT1 functions in cell growth and differentiation. Congenital WT1 mutations predispose to Wilms tumor (a tumor of the kidneys), and are observed in individuals with Denys-Drash Syndrome, Frasier Syndrome and WAGR (Wilms tumour, aniridia [absence of iris], genitourinary anomalies and retardation). A combination of germline and somatic mutations are observed in a subset of Wilms tumor where they are almost invariably homozygous - resulting in inactivation of WT1. Somatic WT1 mutations are present in acute and chronic myeloid leukemia, myelodysplastic syndrome and other blood neoplasms (including acute lymphoblastic leukemia). Wilms tumors display WT1 expression similar to fetal kidney, consistent with the fetal origin of Wilms tumors.

In mice, germline knockout of WT1 (Wt1-/-) results in apoptosis of intermediate mesoderm and subsequent failure of kidney and gonadal development. Wt1-/- embryos die during fetal development or at birth, depending upon strain background. Somatic mosaic inactivation of Wt1 results in the development of Wilms tumor in the background of biallelic expression of the normally imprinted Igf2 gene

The Wt1 floxed allele (Wt1^flox) has loxP sites flanking Wt1 exons 8-9 (encoding the second and third of the four DNA-binding zinc-finger domains). Mice homozygous for this floxed allele (Wt1^flox/flox) are viable and fertile with no reported gross physical or behavioral abnormalities. The donating investigator reports that homozygotes have normal expression levels of WT1 mRNA and protein.

When bred to mice that express Cre recombinase, the resulting offspring will have the floxed region deleted in cre-expressing tissues. The deletion allele (Wt1^Δ) encodes an in-frame truncated protein that is expressed at levels similar to endogenous WT1, but the Wt1^Δ protein is non-functional. Homozygous deletion (Wt1^Δ/Δ) embryos are phenotypically like Wt1-/- embryos - consistent with Wt1^Δ being a loss-of-function allele.

Development

The Wt1^flox allele was created in the laboratory of Dr. Vicki Huff (University of Texas, M. D. Anderson Cancer Center) to have loxP sites flanking exons 8-9. First, a targeting vector was designed to place a loxP site upstream of exon 8, and a loxP-flanked neo cassette just downstream of exon 9 of the Wilms tumor 1 homolog locus (Wt1) on chromosome 2. The construct was electroporated into 129S7/SvEvBrd-Hprt⁺-derived AB1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts, and chimeric males were bred with C57BL/6 females to establish the colony. The resulting Wt1^neo-loxP mice were bred with CMV-Cre transgenic mice (unspecified genetic background), and offspring with germline deletion of the neo cassette, but retaining the loxP-flanked exons 8-9, were selected (and the cre-expressing transgene was removed). The donating investigator reports Wt1^flox mice (mixed C57BL/6;129 genetic background) were bred together for several years as homozygotes prior to sending males to The Jackson Laboratory Repository in 2017. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).

Control Suggestions

Wild-type from the colony

Approximate Controls

101045 B6129SF2/J

Additional Information

Considerations for Choosing Controls

Selected References

Gao F; Maiti S; Alam N; Zhang Z; Deng JM; Behringer RR; Lecureuil C; Guillou F; Huff V. 2006. The Wilms tumor gene, Wt1, is required for Sox9 expression and maintenance of tubular architecture in the developing testis. Proc Natl Acad Sci U S A 103(32):11987-92PubMed: 16877546 MGI: J:111787

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Genetics

Wt1^tm2Vih

Allele Symbol: Wt1^tm2Vih

Allele Name	targeted mutation 2, Vicki Huff
Allele Type	Targeted (Conditional ready (e.g. floxed), No functional change)
Allele Synonym(s)	Wt1^flox; Wt1^fx
Gene Symbol and Name	Wt1, Wilms tumor 1 homolog
Gene Synonym(s)
Strain of Origin	129S7/SvEvBrd-Hprt⁺
Chromosome	2
Molecular Note	Exons 8 and 9 were flanked by loxP sites and a neo resistance cassette with a loxP site was inserted downstream of the floxed exons via homologous recombination. The neo cassette was removed by mating with CMV-Cre transgenic mice.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Cancer Research
- Cre-lox System
  - loxP-flanked Sequences
- Increased Tumor Incidence
  - Leukemia
- Chronic Myelogenous Leukemia
Cell Biology Research
- Transcriptional Regulation
Developmental Biology Research
- Internal/Organ Defects
  - urogenital
  - kidney
Research Tools
- Cancer Research
  - Leukemia
  - Cre-lox System
- Cardiovascular Research
  - Cre-lox System
- Cre-lox System
  - loxP-flanked Sequences
- Developmental Biology Research
  - Cre-lox System
- Genetics Research
  - Mutagenesis and Transgenesis: Cre-lox System
- Reproductive Biology Research
  - Cre-lox System
Endocrine Deficiency Research
- Kidney Defects
Internal/Organ Research
- Kidney Defects

Mammalian Phenotype Terms by Genotype

References

Gao F; Maiti S; Alam N; Zhang Z; Deng JM; Behringer RR; Lecureuil C; Guillou F; Huff V. 2006. The Wilms tumor gene, Wt1, is required for Sox9 expression and maintenance of tubular architecture in the developing testis. Proc Natl Acad Sci U S A 103(32):11987-92PubMed: 16877546 MGI: J:111787

Additional - Wt1^tm2Vih related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Wt1
- Genotyping resources and troubleshooting
Breeding Considerations

Mice homozygous for this floxed allele (Wt1^flox/flox) are viable and fertile with no reported gross physical or behavioral abnormalities. When maintaining a live colony, heterozygous mice may be bred together, to wildtype mice from the colony or to C57BL/6J inbred mice (Stock No. 000664). Alternatively, homozygous mice may be bred together.
- Additional Breeding and Husbandry Support
Mating System
- Homozygote x Homozygote
Citation
When using the Wt1^flox mouse strain in a publication, please cite the originating article(s) and include JAX stock #019554 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous for Wt1<tm2Vih>

Related Products and Services

Frozen Mouse Embryo	STOCK Wt1<tm2Vih>/J	$2595.00
Frozen Mouse Embryo	STOCK Wt1<tm2Vih>/J	$2595.00
Frozen Mouse Embryo	STOCK Wt1<tm2Vih>/J	$3373.50
Frozen Mouse Embryo	STOCK Wt1<tm2Vih>/J	$3373.50

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The Jackson Laboratory's Genotype Promise

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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Also Known As:Wt1flox

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Wt1tm2Vih

Allele Symbol: Wt1tm2Vih

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

References

Additional - Wt1tm2Vih related

Genotyping Protocols

Breeding Considerations

Mating System

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

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^flox

Wt1^tm2Vih

Allele Symbol: Wt1^tm2Vih

Additional - Wt1^tm2Vih related