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 Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation +N1p Generation Definitions   Donating Investigator Dr. Rudolf Jaenisch,   Whitehead Institute (MIT)

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).

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

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 breeding the Wt1^tm1Jae mutation to C57BL/6J mice (Stock No. 000664).

Control Information

	Control
	Wild-type from the colony
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls

Related Strains

Strains carrying   Wt1^tm1Jae allele

002719	B6.129S4-Wt1tm1Jae/J
006817	D2.129S4(Cg)-Wt1tm1Jae/EiJ

View Strains carrying   Wt1^tm1Jae     (2 strains)

Strains carrying other alleles of Wt1

010911	STOCK Wt1tm1(EGFP/cre)Wtp/J
010912	STOCK Wt1tm2(cre/ERT2)Wtp/J

View Strains carrying other alleles of Wt1     (2 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- 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)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Wt1^tm1Jae/Wt1^tm1Jae

        involves: 129S4/SvJae * C57BL/6

• mortality/aging
• complete lethality throughout fetal growth and development
  • death between E13 and E15; no homozygous embryos are recovered after E15.5   (MGI Ref ID J:14317)
• cardiovascular system phenotype
• *normal* cardiovascular system phenotype
  • normal aortic, pulmonary, mitral, and tricuspid valves   (MGI Ref ID J:14317)
  • normal atrial and ventricular septa   (MGI Ref ID J:14317)
• • abnormal heart shape
    • rounded apex   (MGI Ref ID J:14317)
  • hemopericardium
    • small amount of pericardial blood observed in some mice   (MGI Ref ID J:14317)
  • small heart   (MGI Ref ID J:14317)
• embryogenesis phenotype
• abnormal embryonic tissue morphology   (MGI Ref ID J:14317)
• • abnormal gonadal ridge morphology
    • retarded development of the gonadal ridge followed by arrest around E14   (MGI Ref ID J:14317)
• homeostasis/metabolism phenotype
• edema
  • systemic edema   (MGI Ref ID J:14317)
• hemopericardium
  • small amount of pericardial blood observed in some mice   (MGI Ref ID J:14317)
• muscle phenotype
• herniated diaphragm
  • incomplete development resulting in the herniation of lung tissue into the abdominal cavity   (MGI Ref ID J:14317)
• renal/urinary system phenotype
• abnormal kidney development
  • arrested development   (MGI Ref ID J:14317)
• • increased metanephric mesenchyme apoptosis
    • degeneration of the metaneprhic blastema observed at E12   (MGI Ref ID J:14317)
    • apoptosis in 10 to 50% of the cells of the metanephric blastema   (MGI Ref ID J:14317)
• respiratory system phenotype
• abnormal lung development
  • impeded growth, putatively due to incomplete pleura expansion   (MGI Ref ID J:14317)
• cellular phenotype
• increased metanephric mesenchyme apoptosis
  • degeneration of the metaneprhic blastema observed at E12   (MGI Ref ID J:14317)
  • apoptosis in 10 to 50% of the cells of the metanephric blastema   (MGI Ref ID J:14317)

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 * MF1

• mortality/aging
• complete perinatal lethality
  • approximately 16% of homozygous offsrping from intercrosses of heterozygous F1 mice survive to birth, but died immediately after due to impaired lung inflation approximately 16% survived to birth, but died immediately after due to impaired lung inflation   (MGI Ref ID J:56651)
• partial prenatal lethality
  • some embryos die in utero   (MGI Ref ID J:56651)
• endocrine/exocrine gland phenotype
• absent adrenal gland
  • observed at E18.5 in mice on a background involving MF1   (MGI Ref ID J:56651)
• hematopoietic system phenotype
• abnormal spleen development
  • spleen primordium is smaller at E13.5 and the connection to the prospective pancreas is shortened   (MGI Ref ID J:56651)
  • at E15.5, only some thickening of the mesogastrium is observed and not a well-developed spleen as in wild-type   (MGI Ref ID J:56651)
  • stromal cells fo the spleen fail to develop   (MGI Ref ID J:56651)
• absent spleen
  • almost complete absence of the spleen, correlated with increased apoptosis of primordial spleen cells   (MGI Ref ID J:56651)
• increased splenocyte apoptosis
  • increased apoptosis of primordial spleen cells   (MGI Ref ID J:56651)
• immune system phenotype
• abnormal spleen development
  • spleen primordium is smaller at E13.5 and the connection to the prospective pancreas is shortened   (MGI Ref ID J:56651)
  • at E15.5, only some thickening of the mesogastrium is observed and not a well-developed spleen as in wild-type   (MGI Ref ID J:56651)
  • stromal cells fo the spleen fail to develop   (MGI Ref ID J:56651)
• absent spleen
  • almost complete absence of the spleen, correlated with increased apoptosis of primordial spleen cells   (MGI Ref ID J:56651)
• increased splenocyte apoptosis
  • increased apoptosis of primordial spleen cells   (MGI Ref ID J:56651)
• cellular phenotype
• increased splenocyte apoptosis
  • increased apoptosis of primordial spleen cells   (MGI Ref ID J:56651)

Wt1^tm1Jae/Wt1^tm1Jae

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

• mortality/aging
• complete neonatal lethality
  • homozygous offspring from intercrosses of heterozygous F1 mice survive to birth, but die immediately after due to impaired lung inflation   (MGI Ref ID J:56651)
• respiratory system phenotype
• primary atelectasis   (MGI Ref ID J:56651)

Wt1^tm1Jae/Wt1^tm1Jae

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

• mortality/aging
• complete neonatal lethality
  • homozygous offspring from intercrosses of heterozygous F1 mice survive to birth, but die immediately after due to impaired lung inflation   (MGI Ref ID J:56651)
• respiratory system phenotype
• primary atelectasis   (MGI Ref ID J:56651)

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 provided by MGI

Allele Symbol		Wt1tm1Jae
Allele Name		targeted mutation 1, Rudolf Jaenisch
Allele Type		Targeted (knock-out)
Common Name(s)		wt1-;
Mutation Made By		Dr. Rudolf Jaenisch,   Whitehead Institute (MIT)
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)		AWT1; D630046I19Rik; EWS-WT1; GUD; NPHS4; RIKEN cDNA D630046I19 gene; WAGR; WIT-2; WT33; Wt-1;
Molecular Note		Exon 1 and 0.5kb of upstream sequence were replaced with a neomycin selection cassette. [MGI Ref ID J:14317]

Genotyping

Genotyping Information

Genotyping Protocols

Wt1^tm1Jae, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

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

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]

Chen SR; Chen M; Wang XN; Zhang J; Wen Q; Ji SY; Zheng QS; Gao F; Liu YX. 2013. The wilms tumor gene, wt1, maintains testicular cord integrity by regulating the expression of col4a1 and col4a2. Biol Reprod 88(3):56. [PubMed: 23325811]  [MGI Ref ID J:194489]

Christoffels VM; Grieskamp T; Norden J; Mommersteeg MT; Rudat C; Kispert A. 2009. Tbx18 and the fate of epicardial progenitors. Nature 458(7240):E8-9; discussion E9-10. [PubMed: 19369973]  [MGI Ref ID J:147421]

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]

Correa SM; Washburn LL; Kahlon RS; Musson MC; Bouma GJ; Eicher EM; Albrecht KH. 2012. Sex reversal in C57BL/6J XY mice caused by increased expression of ovarian genes and insufficient activation of the testis determining pathway. PLoS Genet 8(4):e1002569. [PubMed: 22496664]  [MGI Ref ID J:183829]

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]

Guadix JA; Ruiz-Villalba A; Lettice L; Velecela V; Munoz-Chapuli R; Hastie ND; Perez-Pomares JM; Martinez-Estrada OM. 2011. Wt1 controls retinoic acid signalling in embryonic epicardium through transcriptional activation of Raldh2. Development 138(6):1093-7. [PubMed: 21343363]  [MGI Ref ID J:170840]

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]

Hu Q; Gao F; Tian W; Ruteshouser EC; Wang Y; Lazar A; Stewart J; Strong LC; Behringer RR; Huff V. 2011. Wt1 ablation and Igf2 upregulation in mice result in Wilms tumors with elevated ERK1/2 phosphorylation. J Clin Invest 121(1):174-83. [PubMed: 21123950]  [MGI Ref ID J:171852]

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]

Norden J; Grieskamp T; Lausch E; van Wijk B; van den Hoff MJ; Englert C; Petry M; Mommersteeg MT; Christoffels VM; Niederreither K; Kispert A. 2010. Wt1 and retinoic acid signaling in the subcoelomic mesenchyme control the development of the pleuropericardial membranes and the sinus horns. Circ Res 106(7):1212-20. [PubMed: 20185795]  [MGI Ref ID J:171035]

Onitsuka I; Tanaka M; Miyajima A. 2010. Characterization and functional analyses of hepatic mesothelial cells in mouse liver development. Gastroenterology 138(4):1525-35, 1535.e1-6. [PubMed: 20080099]  [MGI Ref ID J:161574]

Pazin DE; Albrecht KH. 2009. Developmental expression of Smoc1 and Smoc2 suggests potential roles in fetal gonad and reproductive tract differentiation. Dev Dyn 238(11):2877-90. [PubMed: 19842175]  [MGI Ref ID J:153731]

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]

Sciesielski LK; Kirschner KM; Scholz H; Persson AB. 2010. Wilms' tumor protein Wt1 regulates the Interleukin-10 (IL-10) gene. FEBS Lett 584(22):4665-71. [PubMed: 20974136]  [MGI Ref ID J:167560]

Val P; Martinez-Barbera JP; Swain A. 2007. Adrenal development is initiated by Cited2 and Wt1 through modulation of Sf-1 dosage. Development 134(12):2349-58. [PubMed: 17537799]  [MGI Ref ID J:135126]

Wagner KD; Wagner N; Schley G; Theres H; Scholz H. 2003. The Wilms' tumor suppressor Wt1 encodes a transcriptional activator of the class IV POU-domain factor Pou4f2 (Brn-3b). Gene 305(2):217-23. [PubMed: 12609742]  [MGI Ref ID J:175204]

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

Animal Health Reports

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

Colony Maintenance

Breeding & Husbandry	The B6;129-Wt1tm1Jae strain is maintained by mating heterozygous carriers with wild type mice. Heterozygous breeder pairs are supplied, homozygotes die between embryonic days 13 and 15.
Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

General Supply Notes

• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	Wild-type from the colony
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

See Terms of Use tab for General Terms and Conditions

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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