Strain Name:

FVB.Cg-Tg(Wnt1)1Hev/J

Stock Number:

002934

Availability:

Cryopreserved - Ready for recovery

Use Restrictions Apply, see Terms of Use

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

Former Names FVB/NJ-Tg(Wnt1)1Hev/J    (Changed: 04-MAY-06 )
Type Congenic; Mutant Strain; Transgenic;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Mating System+/+ sibling x Hemizygote         (Female x Male)   02-SEP-09
Specieslaboratory mouse
 
Donating Investigator IMR Colony,   The Jackson Laboratory

Appearance
albino
Related Genotype: Tyrc/Tyrc

Description
Mammary glands from virgin hemizygous females carrying the (Wnt1)1Hev transgene resemble hormonally-stimulated glands from pregnant mice. There was a marked increase in numbers of terminal branches and alveoli, producing a diffuse lobular hyperplasia. Parous transgenic females were unable to lactate. Hemizygous transgenic male glands, while less developed, also were hyperplastic. Adenocarcinomas developed between 3 and 7 months in females and more rarely in males. Occasional metastatic lesions were observed in females. Salivary adenocarcinomas were also occasionally observed in both males and females. Tumors arose stochastically, indicating additional events are required for neoplasia. Subsequent work with Wnt1 transgenic mice includes infection with MMTV to identify contributing oncogenes and mating to transgenic mice bearing other oncogenes.

Development
The construct contained an MMTV LTR about 1 kb upstream from a Wnt1 genomic clone, with SV40 splice and polyadenylation sites added at the 3' end, and was microinjected into (C57BL/6 X SJL)F1 fertilized eggs. The strain was backcrossed to FVB/NJ for 11 generations.

Control Information

  Control
   Noncarrier
   001800 FVB/NJ
 
  Considerations for Choosing Controls

Related Strains

Strains carrying   Tg(Wnt1)1Hev allele
002870   B6SJL-Tg(Wnt1)1Hev/J
View Strains carrying   Tg(Wnt1)1Hev     (1 strain)

Strains carrying other alleles of Wnt1
000243   B6C3Fe a/a-Wnt1sw/J
002865   B6CBA-Tg(Wnt1-lacZ)206Amc/J
003829   STOCK Tg(Wnt1-cre)11Rth Tg(Wnt1-GAL4)11Rth/J
007807   STOCK Tg(Wnt1-cre)11Rth/MileJ
View Strains carrying other alleles of Wnt1     (4 strains)

View Strains carrying other alleles of MMTV     (18 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms
      assigned by genotype

Tg(Wnt1)1Hev/0

        either: FVB/N or (involves: C57BL/6 * SJL)
  • endocrine/exocrine gland phenotype
  • abnormal mammary gland morphology (MGI Ref ID J:28473)
    • mammary glands in virgin females resemble hormonally-stimulated glands from pregnant mice
    • abnormal branching of the mammary ductal tree (MGI Ref ID J:28473)
      • hemizygous transgenic females show a marked increase in the number of terminal branches
    • abnormal mammary gland lobule morphology (MGI Ref ID J:28473)
      • hemizygous transgenic females display diffuse lobular hyperplasia
      • mammary gland alveolar hyperplasia (MGI Ref ID J:28473)
  • reproductive system phenotype
  • abnormal mammary gland morphology (MGI Ref ID J:28473)
    • mammary glands in virgin females resemble hormonally-stimulated glands from pregnant mice
    • abnormal branching of the mammary ductal tree (MGI Ref ID J:28473)
      • hemizygous transgenic females show a marked increase in the number of terminal branches
    • abnormal mammary gland lobule morphology (MGI Ref ID J:28473)
      • hemizygous transgenic females display diffuse lobular hyperplasia
      • mammary gland alveolar hyperplasia (MGI Ref ID J:28473)

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

Tg(Wnt1)1Hev/0

        involves: C57BL/6 * FVB * SJL
  • endocrine/exocrine gland phenotype
  • abnormal branching of the mammary ductal tree (MGI Ref ID J:96305)
    • mammary glands of virgin females have excessive ductal side branching resembling that of pregnant wild-type mice
  • mammary gland hyperplasia (MGI Ref ID J:96305)
    • mammary glands of virgin females have extensive, dense hyperplasia
  • reproductive system phenotype
  • abnormal branching of the mammary ductal tree (MGI Ref ID J:96305)
    • mammary glands of virgin females have excessive ductal side branching resembling that of pregnant wild-type mice
  • mammary gland hyperplasia (MGI Ref ID J:96305)
    • mammary glands of virgin females have extensive, dense hyperplasia
  • tumorigenesis
  • mammary gland tumor (MGI Ref ID J:96305)
    • develop mammary tumors
View Research Applications

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

Cancer Research
Increased Tumor Incidence
      Mammary Gland Tumors

Genes & Alleles

Gene & Allele Information

 
Allele Symbol Tg(Wnt1)1Hev
Allele Name transgene insertion 1, Harold E Varmus
Allele Type Transgenic (random, expressed)
Common Name(s) MMTV-Wnt-1; Wnt-1; line 303;
Mutation Made By Harold Varmus,   Memorial Sloan-Kettering Cancer Center
Strain of OriginC57BL/6 x SJL
Expressed Gene Wnt1, wingless-related MMTV integration site 1, mouse, laboratory
Promoter MMTV, Mouse Mammary Tumor Virus, MMTV
Molecular Note Wnt1 is driven by the mouse mammary tumor virus (MMTV). The construct resembles alleles found in virus-induced tumors. [MGI Ref ID J:28473]
 
 

Genotyping

Genotyping Information

Genotyping Protocols

Tg(Wnt1)1Hev, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References

Selected Reference(s)

Tsukamoto AS; Grosschedl R; Guzman RC; Parslow T; Varmus HE. 1988. Expression of the int-1 gene in transgenic mice is associated with mammary gland hyperplasia and adenocarcinomas in male and female mice. Cell 55(4):619-25. [PubMed: 3180222]  [MGI Ref ID J:28473]

Additional References

Tg(Wnt1)1Hev related

Alexander CM; Reichsman F; Hinkes MT; Lincecum J; Becker KA; Cumberledge S; Bernfield M. 2000. Syndecan-1 is required for wnt-1-induced mammary tumorigenesis in mice Nat Genet 25(3):329-32. [PubMed: 10888884]  [MGI Ref ID J:63122]

Bocchinfuso WP; Hively WP; Couse JF; Varmus HE; Korach KS. 1999. A mouse mammary tumor virus-Wnt-1 transgene induces mammary gland hyperplasia and tumorigenesis in mice lacking estrogen receptor-alpha. Cancer Res 59(8):1869-76. [PubMed: 10213494]  [MGI Ref ID J:54215]

Brisken C; Heineman A; Chavarria T; Elenbaas B; Tan J; Dey SK; McMahon JA; McMahon AP; Weinberg RA. 2000. Essential function of Wnt-4 in mammary gland development downstream of progesterone signaling. Genes Dev 14(6):650-4. [PubMed: 10733525]  [MGI Ref ID J:61384]

Broccoli D; Godley LA; Donehower LA; Varmus HE; de Lange T. 1996. Telomerase activation in mouse mammary tumors: lack of detectable telomere shortening and evidence for regulation of telomerase RNA with cell proliferation. Mol Cell Biol 16(7):3765-72. [PubMed: 8668193]  [MGI Ref ID J:71575]

Bulavin DV; Phillips C; Nannenga B; Timofeev O; Donehower LA; Anderson CW; Appella E; Fornace AJ Jr. 2004. Inactivation of the Wip1 phosphatase inhibits mammary tumorigenesis through p38 MAPK-mediated activation of the p16(Ink4a)-p19(Arf) pathway. Nat Genet 36(4):343-50. [PubMed: 14991053]  [MGI Ref ID J:121570]

Cao Y; Luo JL; Karin M. 2007. IkappaB kinase alpha kinase activity is required for self-renewal of ErbB2/Her2-transformed mammary tumor-initiating cells. Proc Natl Acad Sci U S A 104(40):15852-7. [PubMed: 17890319]  [MGI Ref ID J:125555]

Cho RW; Wang X; Diehn M; Shedden K; Chen GY; Sherlock G; Gurney A; Lewicki J; Clarke MF. 2008. Isolation and molecular characterization of cancer stem cells in MMTV-Wnt-1 murine breast tumors. Stem Cells 26(2):364-71. [PubMed: 17975224]  [MGI Ref ID J:144892]

Donehower LA; Godley LA; Aldaz CM; Pyle R; Shi YP; Pinkel D; Gray J; Bradley A; Medina D; Varmus HE. 1995. Deficiency of p53 accelerates mammary tumorigenesis in Wnt-1 transgenic mice and promotes chromosomal instability. Genes Dev 9(7):882-95. [PubMed: 7705663]  [MGI Ref ID J:24407]

Du Z; Podsypanina K; Huang S; McGrath A; Toneff MJ; Bogoslovskaia E; Zhang X; Moraes RC; Fluck M; Allred DC; Lewis MT; Varmus HE; Li Y. 2006. Introduction of oncogenes into mammary glands in vivo with an avian retroviral vector initiates and promotes carcinogenesis in mouse models. Proc Natl Acad Sci U S A 103(46):17396-401. [PubMed: 17090666]  [MGI Ref ID J:117125]

Glover CE; Gurley KE; Kim KH; Storer B; Fero ML; Kemp CJ. 2009. Endocrine dysfunction in p27Kip1 deficient mice and susceptibility to Wnt-1 driven breast cancer. Carcinogenesis 30(6):1058-63. [PubMed: 19380520]  [MGI Ref ID J:149486]

Huang S; Li Y; Chen Y; Podsypanina K; Chamorro M; Olshen AB; Desai KV; Tann A; Petersen D; Green JE; Varmus HE. 2005. Changes in gene expression during the development of mammary tumors in MMTV-Wnt-1 transgenic mice. Genome Biol 6(10):R84. [PubMed: 16207355]  [MGI Ref ID J:103821]

Jones JM; Attardi L; Godley LA; Laucirica R; Medina D; Jacks T ; Varmus HE ; Donehower LA. 1997. Absence of p53 in a mouse mammary tumor model promotes tumor cell proliferation without affecting apoptosis. Cell Growth Differ 8(8):829-38. [PubMed: 9269892]  [MGI Ref ID J:43335]

Kim YC; Clark RJ; Ranheim EA; Alexander CM. 2008. Wnt1 expression induces short-range and long-range cell recruitments that modify mammary tumor development and are not induced by a cell-autonomous beta-catenin effector. Cancer Res 68(24):10145-53. [PubMed: 19074881]  [MGI Ref ID J:142240]

Kouros-Mehr H; Bechis SK; Slorach EM; Littlepage LE; Egeblad M; Ewald AJ; Pai SY; Ho IC; Werb Z. 2008. GATA-3 links tumor differentiation and dissemination in a luminal breast cancer model. Cancer Cell 13(2):141-52. [PubMed: 18242514]  [MGI Ref ID J:131913]

Kwan H; Pecenka V; Tsukamoto A; Parslow TG; Guzman R; Lin TP; Muller WJ; Lee FS; Leder P; Varmus HE. 1992. Transgenes expressing the Wnt-1 and int-2 proto-oncogenes cooperate during mammary carcinogenesis in doubly transgenic mice. Mol Cell Biol 12(1):147-54. [PubMed: 1530875]  [MGI Ref ID J:1811]

Lane TF; Leder P. 1997. Wnt-10b directs hypermorphic development and transformation in mammary glands of male and female mice. Oncogene 15(18):2133-44. [PubMed: 9393971]  [MGI Ref ID J:44244]

Li Y, Podsypanina K, Liu X, Crane A, Tan LK, Parsons R, Varmus HE.. 2001. Deficiency of Pten accelerates mammary oncogenesis in MMTV-Wnt-1 transgenic mice. BMC Mol Biol 2(1):2. [PubMed: 11178110]  [MGI Ref ID J:67497]

Li Y; Welm B; Podsypanina K; Huang S; Chamorro M; Zhang X; Rowlands T; Egeblad M; Cowin P; Werb Z; Tan LK; Rosen JM; Varmus HE. 2003. Evidence that transgenes encoding components of the Wnt signaling pathway preferentially induce mammary cancers from progenitor cells. Proc Natl Acad Sci U S A 100(26):15853-8. [PubMed: 14668450]  [MGI Ref ID J:87520]

Lindvall C; Evans NC; Zylstra CR; Li Y; Alexander CM; Williams BO. 2006. The Wnt signaling receptor Lrp5 is required for mammary ductal stem cell activity and Wnt1-induced tumorigenesis. J Biol Chem 281(46):35081-7. [PubMed: 16973609]  [MGI Ref ID J:115934]

Lindvall C; Zylstra CR; Evans N; West RA; Dykema K; Furge KA; Williams BO. 2009. The Wnt co-receptor Lrp6 is required for normal mouse mammary gland development. PLoS One 4(6):e5813. [PubMed: 19503830]  [MGI Ref ID J:150203]

Marino S; Romelfanger C; Yokota Y; Nusse R. 2004. Wnt1 is epistatic to Id2 in inducing mammary hyperplasia, ductal side-branching, and tumors in the mouse. BMC Cancer 4(1):91. [PubMed: 15601467]  [MGI Ref ID J:96305]

Podsypanina K; Li Y; Varmus HE. 2004. Evolution of somatic mutations in mammary tumors in transgenic mice is influenced by the inherited genotype. BMC Med 2(1):24. [PubMed: 15198801]  [MGI Ref ID J:91649]

Reddy HK; Mettus RV; Rane SG; Grana X; Litvin J; Reddy EP. 2005. Cyclin-dependent kinase 4 expression is essential for neu-induced breast tumorigenesis. Cancer Res 65(22):10174-8. [PubMed: 16288002]  [MGI Ref ID J:103411]

Schroeder JA; Adriance MC; Thompson MC; Camenisch TD; Gendler SJ. 2003. MUC1 alters beta-catenin-dependent tumor formation and promotes cellular invasion. Oncogene 22(9):1324-32. [PubMed: 12618757]  [MGI Ref ID J:82470]

Shackleford GM; MacArthur CA; Kwan HC; Varmus HE. 1993. Mouse mammary tumor virus infection accelerates mammary carcinogenesis in Wnt-1 transgenic mice by insertional activation of int-2/Fgf-3 and hst/Fgf-4. Proc Natl Acad Sci U S A 90(2):740-4. [PubMed: 8380647]  [MGI Ref ID J:3728]

Shekhar MP; Gerard B; Pauley RJ; Williams BO; Tait L. 2008. Rad6B is a positive regulator of beta-catenin stabilization. Cancer Res 68(6):1741-50. [PubMed: 18339854]  [MGI Ref ID J:150916]

Teissedre B ; Pinderhughes A ; Incassati A ; Hatsell SJ ; Hiremath M ; Cowin P. 2009. MMTV-Wnt1 and -DeltaN89beta-catenin induce canonical signaling in distinct progenitors and differentially activate Hedgehog signaling within mammary tumors. PLoS ONE 4(2):e4537. [PubMed: 19225568]  [MGI Ref ID J:146601]

Vaillant F; Asselin-Labat ML; Shackleton M; Forrest NC; Lindeman GJ; Visvader JE. 2008. The mammary progenitor marker CD61/beta3 integrin identifies cancer stem cells in mouse models of mammary tumorigenesis. Cancer Res 68(19):7711-7. [PubMed: 18829523]  [MGI Ref ID J:141826]

Yu Q; Geng Y; Sicinski P. 2001. Specific protection against breast cancers by cyclin D1 ablation. Nature 411(6841):1017-21. [PubMed: 11429595]  [MGI Ref ID J:70276]

Yue W; Santen RJ; Wang JP; Li Y; Verderame MF; Bocchinfuso WP; Korach KS; Devanesan P; Todorovic R; Rogan EG; Cavalieri EL. 2003. Genotoxic metabolites of estradiol in breast: potential mechanism of estradiol induced carcinogenesis. J Steroid Biochem Mol Biol 86(3-5):477-86. [PubMed: 14623547]  [MGI Ref ID J:86738]

Zhang X; Podsypanina K; Huang S; Mohsin SK; Chamness GC; Hatsell S; Cowin P; Schiff R; Li Y. 2005. Estrogen receptor positivity in mammary tumors of Wnt-1 transgenic mice is influenced by collaborating oncogenic mutations. Oncogene 24(26):4220-31. [PubMed: 15824740]  [MGI Ref ID J:99546]

Zhao H; Cui Y; Dupont J; Sun H; Hennighausen L; Yakar S. 2005. Overexpression of the tumor suppressor gene phosphatase and tensin homologue partially inhibits wnt-1-induced mammary tumorigenesis. Cancer Res 65(15):6864-73. [PubMed: 16061670]  [MGI Ref ID J:100768]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Mating System+/+ sibling x Hemizygote         (Female x Male)   02-SEP-09
Diet Information LabDiet® 5K52/5K67

Purchasing information

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

Pricing

Pricing for USA, Canada and Mexico shipping destinations View International pricing
Price (US dollars $)
Cryorecovery Fee $1900.00
Cryopreserved Embryos $1600.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Additional Supply Details

Pricing for International shipping destinations View USA Canada and Mexico pricing
Price (US dollars $)
Cryorecovery Fee $2470.00
Cryopreserved Embryos $2080.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Additional Supply Details

Supply Details

Standard SupplyCryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information.
Supply Notes
  • Cryopreserved Embryos
    This strain is also available as cryopreserved embryos. Orders for cryopreserved embryos may be placed with our Customer Service Department. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos, please visit our Cryopreserved Embryos web page.
  • Cryorecovery - Standard.
    We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. The total number of animals provided, their gender and genotype will vary. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 13 and 16 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of 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 about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory 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. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

  • 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
   Noncarrier
   001800 FVB/NJ
 
  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.

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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.
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