Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Background Strain C57BL/6J Donor Strain 129S4 via J1 ES cell line Generation N20pN1   Donating Investigator IMR Colony,   The Jackson Laboratory

Appearance
black
Related Genotype: a/a

Description
Mice homozygous for the Wt1^tm1Jae targeted mutation die between embryonic days 13 and 15. They fail to develop a kidney or gonads. The hearts of homozygous mutant mice also fail to develop properly. Hearts are smaller than wildtype controls and possess a rounded apex. The right ventricular wall is thin and the left ventricle is reduced in size. There appears to be normal development of the aortic, pulmonary, mitral and tricuspid valves. Development of the diaphragm is also incomplete resulting in incomplete separation of the thoracic and abdominal cavities. Homozygous mutant lungs are also markedly smaller than wild type lungs. Heterozygous mice appear normal and show no tumor development (mice followed until 10 months of age).

Development
This targeted mutant was made in the Laboratory of Dr. Rudolf Jaenisch at the Whitehead Institute for Biomedical Research. A replacement-type targeting vector was used which resulted in the deletion of the first exon and 0.5 kb of upstream sequence. Targeting was done in J1 ES cells. This strain was produced by backcrossing the Wt1^tm1Jae mutation to C57BL/6J. Currently N6 (April, 1997)

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying   Wt1^tm1Jae allele

002332	B6;129S4-Wt1tm1Jae/J
006817	D2.129S4(Cg)-Wt1tm1Jae/EiJ

View Strains carrying   Wt1^tm1Jae     (2 strains)

Additional Web Information

Congenic Nomenclature
Genetic Quality Control Annual Report

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Wt1^tm1Jae/Wt1^tm1Jae

        involves: 129S4/SvJae * C57BL/6

• lethality-prenatal/perinatal
• lethality throughout fetal growth and development (MGI Ref ID J:14317)
  • death between E13 and E15
• cardiovascular system phenotype
• *normal* cardiovascular system phenotype (MGI Ref ID J:14317)
  • normal aortic, pulmonary, mitral, and tricuspid valves
  • normal atrial and ventricular septa
• abnormal heart shape (MGI Ref ID J:14317)
  • rounded apex
• hemopericardium (MGI Ref ID J:14317)
  • small amount of pericardial blood observed in some mice
• small heart (MGI Ref ID J:14317)
• cellular phenotype
• abnormal apoptosis (MGI Ref ID J:14317)
  • apoptosis of in 10 to 50% of the cells of the metanephric blastema
• embryogenesis phenotype
• abnormal embryonic tissue morphology (MGI Ref ID J:14317)
• homeostasis/metabolism phenotype
• edema (MGI Ref ID J:14317)
  • systemic edema
• muscle phenotype
• herniated diaphragm (MGI Ref ID J:14317)
  • incomplete development resulting in the herniation of lung tissue into the abdominal cavity
• renal/urinary system phenotype
• abnormal kidney development (MGI Ref ID J:14317)
  • arrested development
  • degeneration of the metaneprhic blastema observed at E12
• reproductive system phenotype
• abnormal primary sex determination (MGI Ref ID J:14317)
  • retarded development of the gonadal ridge followed by arrest around E14
• respiratory system phenotype
• abnormal lung development (MGI Ref ID J:14317)
  • impeded growth, putatively due to incomplete pleura expansion

Wt1^tm1Jae/Wt1^tm1Jae

        involves: 129S4/SvJae * C57BL/6 * MF1

• lethality-prenatal/perinatal
• perinatal lethality (MGI Ref ID J:56651)
  • approximately 16% survived to birth, but died immediately after due to impaired lung inflation
• prenatal lethality (MGI Ref ID J:56651)
  • approximately 84% of embryos died in utero
• cellular phenotype
• abnormal apoptosis (MGI Ref ID J:56651)
  • increased apoptosis of primordial spleen cells
• endocrine/exocrine gland phenotype
• absent adrenal gland (MGI Ref ID J:56651)
  • observed at E18.5 in mice on a background involving MF1
• hematopoietic system phenotype
• absent spleen (MGI Ref ID J:56651)
  • correlation with increased apoptosis of primordial spleen cells
• immune system phenotype
• absent spleen (MGI Ref ID J:56651)
  • correlation with increased apoptosis of primordial spleen cells

Wt1^tm1Jae/Wt1^tm1Jae

        involves: 129S4/SvJae * BALB/c * C57BL/6

• lethality-prenatal/perinatal
• neonatal lethality (MGI Ref ID J:56651)
  • survived to birth, but died immediately after due to impaired lung inflation

Wt1^tm1Jae/Wt1^tm1Jae

        involves: 129S4/SvJae * C3H * C57BL/6

• lethality-prenatal/perinatal
• neonatal lethality (MGI Ref ID J:56651)
  • survived to birth, but died immediately after due to impaired lung inflation

View Research Applications

Research Applications

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

Wt1^tm1Jae related

Cancer Research
Tumor Suppressor Genes

Cardiovascular Research
Heart Abnormalities

Developmental Biology Research
Internal/Organ Defects (kidneys, gonads, heart)

Internal/Organ Research
Heart Abnormalities
Kidney Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Wt1tm1Jae
Allele Name		targeted mutation 1, Rudolf Jaenisch
Allele Type		Targeted (knock-out)
Common Name(s)		wt1-;
Mutation Made By		Rudolf Jaenisch,   Massachusetts Institute of Technology
Strain of Origin		129S4/SvJae
ES Cell Line Name		J1
ES Cell Line Strain		129S4/SvJae
Gene Symbol and Name		Wt1, Wilms tumor 1 homolog
Chromosome		2
Gene Common Name(s)		D630046I19Rik; GUD; RIKEN cDNA D630046I19 gene; WAGR; WIT-2; WT33; Wt-1;
Molecular Note		Exon 1 and 0.5kb of upstream sequence were deleted by the insertion of a neomycin selection cassette. [MGI Ref ID J:14317]

Genotyping

Genotyping Information

Genotyping Protocols

NEOTD (Generic Neo), STD PCR, vers. 1
Wt1^tm1Jae, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Kreidberg JA; Sariola H; Loring JM; Maeda M; Pelletier J; Housman D; Jaenisch R. 1993. WT-1 is required for early kidney development. Cell 74(4):679-91. [PubMed: 8395349]  [MGI Ref ID J:14317]

Additional References

Discenza MT; He S; Lee TH; Chu LL; Bolon B; Goodyer P; Eccles M; Pelletier J. 2003. WT1 is a modifier of the Pax2 mutant phenotype: cooperation and interaction between WT1 and Pax2. Oncogene 22(50):8145-55. [PubMed: 14603255]  [MGI Ref ID J:86661]

Wilhelm D; Englert C. 2002. The Wilms tumor suppressor WT1 regulates early gonad development by activation of Sf1. Genes Dev 16(14):1839-51. [PubMed: 12130543]  [MGI Ref ID J:77996]

Wt1^tm1Jae related

Brennan J; Capel B. 2004. One tissue, two fates: molecular genetic events that underlie testis versus ovary development. Nat Rev Genet 5(7):509-21. [PubMed: 15211353]  [MGI Ref ID J:90770]

Chang H; Gao F; Guillou F; Taketo MM; Huff V; Behringer RR. 2008. Wt1 negatively regulates {beta}-catenin signaling during testis development. Development 135(10):1875-85. [PubMed: 18403409]  [MGI Ref ID J:134687]

Clugston RD; Klattig J; Englert C; Clagett-Dame M; Martinovic J; Benachi A; Greer JJ. 2006. Teratogen-induced, dietary and genetic models of congenital diaphragmatic hernia share a common mechanism of pathogenesis. Am J Pathol 169(5):1541-9. [PubMed: 17071579]  [MGI Ref ID J:114565]

Dame C; Kirschner KM; Bartz KV; Wallach T; Hussels CS; Scholz H. 2006. Wilms tumor suppressor, Wt1, is a transcriptional activator of the erythropoietin gene. Blood 107(11):4282-90. [PubMed: 16467207]  [MGI Ref ID J:132868]

Discenza MT; He S; Lee TH; Chu LL; Bolon B; Goodyer P; Eccles M; Pelletier J. 2003. WT1 is a modifier of the Pax2 mutant phenotype: cooperation and interaction between WT1 and Pax2. Oncogene 22(50):8145-55. [PubMed: 14603255]  [MGI Ref ID J:86661]

Donovan MJ; Natoli TA; Sainio K; Amstutz A; Jaenisch R; Sariola H; Kreidberg JA. 1999. Initial differentiation of the metanephric mesenchyme is independent of WT1 and the ureteric bud. Dev Genet 24(3-4):252-62. [PubMed: 10322633]  [MGI Ref ID J:54493]

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):11987-92. [PubMed: 16877546]  [MGI Ref ID J:111787]

Guo JK; Ardito TA; Kashgarian M; Krause DS. 2006. Prevention of mesangial sclerosis by bone marrow transplantation. Kidney Int 70(5):910-3. [PubMed: 16850025]  [MGI Ref ID J:136487]

Herzer U; Crocoll A; Barton D; Howells N; Englert C. 1999. The Wilms tumor suppressor gene wt1 is required for development of the spleen. Curr Biol 9(15):837-40. [PubMed: 10469569]  [MGI Ref ID J:56651]

Ijpenberg A; Perez-Pomares JM; Guadix JA; Carmona R; Portillo-Sanchez V; Macias D; Hohenstein P; Miles CM; Hastie ND; Munoz-Chapuli R. 2007. Wt1 and retinoic acid signaling are essential for stellate cell development and liver morphogenesis. Dev Biol 312(1):157-70. [PubMed: 18028902]  [MGI Ref ID J:130203]

Kirschner KM; Hagen P; Hussels CS; Ballmaier M; Scholz H; Dame C. 2008. The Wilms' tumor suppressor Wt1 activates transcription of the erythropoietin receptor in hematopoietic progenitor cells. FASEB J 22(8):2690-701. [PubMed: 18424770]  [MGI Ref ID J:137969]

Klattig J; Sierig R; Kruspe D; Besenbeck B; Englert C. 2007. Wilms' tumor protein Wt1 is an activator of the anti-Mullerian hormone receptor gene Amhr2. Mol Cell Biol 27(12):4355-64. [PubMed: 17420277]  [MGI Ref ID J:122350]

Kreidberg JA; Natoli TA; McGinnis L; Donovan M; Biggers JD; Amstutz A. 1999. Coordinate action of Wt1 and a modifier gene supports embryonic survival in the oviduct. Mol Reprod Dev 52(4):366-75. [PubMed: 10092116]  [MGI Ref ID J:53364]

Lahiri D; Dutton JR; Duarte A; Moorwood K; Graham CF; Ward A. 2007. Nephropathy and defective spermatogenesis in mice transgenic for a single isoform of the Wilms' tumour suppressor protein, WT1-KTS, together with one disrupted Wt1 allele. Mol Reprod Dev 74(3):300-11. [PubMed: 16967512]  [MGI Ref ID J:119219]

Menke AL; Clarke AR; Leitch A; Ijpenberg A; Williamson KA; Spraggon L; Harrison DJ; Hastie ND. 2002. Genetic Interactions between the Wilms' Tumor 1 Gene and the p53 Gene. Cancer Res 62(22):6615-20. [PubMed: 12438257]  [MGI Ref ID J:80297]

Menke AL; IJpenberg A; Fleming S; Ross A; Medine CN; Patek CE; Spraggon L; Hughes J; Clarke AR; Hastie ND. 2003. The wt1-heterozygous mouse; a model to study the development of glomerular sclerosis. J Pathol 200(5):667-74. [PubMed: 12898605]  [MGI Ref ID J:84867]

Moore AW; McInnes L; Kreidberg J; Hastie ND; Schedl A. 1999. YAC complementation shows a requirement for Wt1 in the development of epicardium, adrenal gland and throughout nephrogenesis. Development 126(9):1845-57. [PubMed: 10101119]  [MGI Ref ID J:52756]

Naz RK; Rajesh C. 2005. Gene knockouts that cause female infertility: search for novel contraceptive targets Front Biosci 10:2447-2459. [PubMed: 15970507]  [MGI Ref ID J:103183]

Sainio K; Hellstedt P; Kreidberg JA; Saxen L; Sariola H. 1997. Differential regulation of two sets of mesonephric tubules by WT-1. Development 124(7):1293-9. [PubMed: 9118800]  [MGI Ref ID J:40389]

Wagner KD; Wagner N; Vidal VP; Schley G; Wilhelm D; Schedl A; Englert C; Scholz H. 2002. The Wilms' tumor gene Wt1 is required for normal development of the retina. EMBO J 21(6):1398-405. [PubMed: 11889045]  [MGI Ref ID J:75445]

Wagner N; Wagner KD; Theres H; Englert C; Schedl A; Scholz H. 2005. Coronary vessel development requires activation of the TrkB neurotrophin receptor by the Wilms' tumor transcription factor Wt1. Genes Dev 19(21):2631-42. [PubMed: 16264195]  [MGI Ref ID J:102417]

Wilhelm D; Englert C. 2002. The Wilms tumor suppressor WT1 regulates early gonad development by activation of Sf1. Genes Dev 16(14):1839-51. [PubMed: 12130543]  [MGI Ref ID J:77996]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	The backgound the strain used in the publication was mixed C57BL/6 x 129. The C57BL/6J-Wt1tm1Jae strain is maintained by mating heterozygous carriers to C57BL/6J mice. Expected coat color from breeding:Black
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. At least two mice that carry the mutation (if it is a mutant strain) will be provided. The total number of animals provided, their gender and genotype will vary. Please inquire if larger numbers of animals with specific genotypes and genders are needed. IMPORTANT NOTE: The genotypes of the 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 for possible genotypes for this specific strain. Animals typically ship within 13 to 16 weeks from your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will typically ship within 25 weeks. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

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.

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Ordering and Purchasing Information

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Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

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