Strain Name:

B6D2-Tg(MMTVTGFA)29Rjc/J

Stock Number:

002373

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

Type Mutant Strain; Transgenic;
Additional information on Genetically Engineered and Mutant Mice.
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Specieslaboratory mouse
GenerationN?+2p+N1
 
Donating Investigator Robert Coffey,   Vanderbilt University Medical Center

Appearance
multiple coat colors
Related Genotype: segregating for Tyrp 1b and Myo5ad

Description
Mice are viable and fertile, although mice of the most extensively studied line lactate insufficiently to support the litter. Virgin transgenic mice show no mammary gland abnormalities prepubertally, but adult virgin mice have considerable alveolar gland hyperplasia. Pregnant transgenic mice show marked proliferation of the stromal cells, and alveolar secretion is markedly increased compared to nontransgnic mice. After multiple pregnancies, isolated adenocarcinomas develop. There is no apparent phenotypic effect in males. In females, transgene expression is localized to the small ducts and alveoli in both virgin and pregnant mice as evidenced by in situ hybridization and by immunohistochemistry. Immunostaining also reveals some stromal staining in the hyperplastic areas. Egfr mRNA expression is also increased in mammary tissues expressing high levels of the transgene. Crosses between TGFA transgenic mice and TGFB1 transgenic mice demonstrate that these growth factors oppose each other's action on mammary gland development. The TGFA transgenic mice may also be useful in crosses with mice carrying mutations in the EGF and EGFR families. The putative tumor-promoter effect of TGFA may also be useful in enhancing the detection of tumor-initiating events and in determining the actions of putative metastases-inducing genes.

Control Information

  Control
   Noncarrier
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of TGFA
002459   B6D2-Tg(MMTVTGFA)254Rjc/J
002953   FVB.Cg-Tg(MMTVTGFA)254Rjc/J
002421   FVB/N-Tg(MtTGFA)100Lmb/J
002422   STOCK Tg(MtTGFA)42Lmb/J
003722   SW.Cg-Tg(MtTGFA)42Lmb/J
View Strains carrying other alleles of TGFA     (5 strains)

View Strains carrying other alleles of MMTV     (19 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms
      assigned by genotype

Tg(MMTVTGFA)29Rjc/0

        involves: C57BL/6 * DBA/2
  • endocrine/exocrine gland phenotype
  • *normal* endocrine/exocrine gland phenotype (MGI Ref ID J:28453)
    • male mice exhibit normal mammary and salivary gland
    • abnormal mammary gland morphology (MGI Ref ID J:28453)
      • after formation of tumors at 3 months, glands are small with minimal secretion in the lumen and the stroma around the glands is abundant but mitosis and dysplasia of the epithelial or stromal cells is not observed
      • stroma between the mammary glands is hyperplastic
      • at 5 months two females develop bilateral swollen, lumpy thoracic mammary glands with abundant alveolar and ductal proliferation containing abundant secretions
      • at 5 months of age, female mice exhibit epithelial and stromal proliferation
      • the female founder mouse developed a mass during pregnancy that receded followed by development of masses in the inguinal fat pad and soft tissues of the upper thorax consisting of adenocarcinoma without metastasis
      • at 4 months of age, female mice develop numerous lumps within thoracic and inguinal areas of the mammary glands with large cystic spaces and abundant secretion within the lumen along with solid hyperplasias
      • female mice exhibit abnormal ductal trees
      • female mice exhibit cystically dilated alveoli
      • abnormal mammary gland growth during pregnancy (MGI Ref ID J:28453)
        • during pregnancy, female mice exhibit increased stromal cell proliferation, more prominent nuclei of epithelial cells, and production of more secretion than in wild-type mice
        • after 3 month, female mice that have been pregnant develop an inguineal mammary fat pad that develops into a circumscribed, firm tumor
        • during pregnancy, female mice exhibit abnormal mammary gland hyperplasia with cysts that are more prominent and secretions that are more inspissated than in wild-type mice
      • mammary gland alveolar hyperplasia (MGI Ref ID J:28453)
        • at day 90
      • mammary gland duct hyperplasia (MGI Ref ID J:28453)
        • at 5 months of age
      • mammary gland hyperplasia (MGI Ref ID J:71696)
        • female mice exhibit lobular development similar to a lactating wild-type mice except that the alveoli are irregular and dilated with interstitial stroma edema and a modest increase in leukocyte infiltration
        • however, nulliparous mice exhibit minimal lobular development and no stromal response
        • virgin females exhibit papillary hyperplasia
  • tumorigenesis
  • mammary gland tumor (MGI Ref ID J:28453)
    • after 3 month, female mice that have been pregnant develop an inguineal mammary fat pad that develops into a circumscribed, firm tumor
    • tumors have fibrous encapsulation with no evidence of local invasion and are composed of numerous well-formed alveoli with rare mitotic figures
    • adenomas develop in multiparous female mice
    • at 17 months, 53% of female mice exhibit solid tumors
    • in 6% of female mice at day 250
    • following treatment with 0.5 mg DMBA at 56 days after birth, 50% of mice develop mammary gland tumors at day 180 and 65% at day 250 compared to only 6% of similarly treated wild-type mice at day 250
    • following treatment with 0.5 mg DMBA at 56 days after birth, mice develop an average of 3.6 tumors per mouse with 60% of tumors arising in the thoracic mammary gland and 31% in the inguinal mammary gland
    • following treatment with 0.5 mg DMBA at 21 days after birth, 50% of mice develop mammary tumors within 250 days at a frequency of 2.4 tumors per mouse compared to no tumor development in similarly treated wild-type mice
    • tumor onset is delayed when mice are treated treatment with 0.5 mg DMBA at 21 days after birth compared to at 56 days after birth
    • mammary adenocarcinoma (MGI Ref ID J:28453)
      • the female founder mouse developed a mass during pregnancy that receded followed by development of masses in the inguinal fat pad and soft tissues of the upper thorax consisting of adenocarcinoma without metastasis
      • solid hyperplasias develop into adenocarcinomas
      • in 40% of female mice
      • following treatment with 0.5 mg DMBA at 21 or 56 days after birth, predominantly mammary adenocarcinomas form with occasional squamous differentiation
  • squamous cell carcinoma (MGI Ref ID J:72080)
    • following treatment with 0.5 mg DMBA at 21 or 56 days after birth, predominantly mammary adenocarcinomas form with occasional squamous differentiation
  • behavior/neurological phenotype
  • abnormal nursing (MGI Ref ID J:28453)
    • females cannot suckle her young
    • females cannot nurse her young
  • reproductive system phenotype
  • abnormal mammary gland morphology (MGI Ref ID J:28453)
    • after formation of tumors at 3 months, glands are small with minimal secretion in the lumen and the stroma around the glands is abundant but mitosis and dysplasia of the epithelial or stromal cells is not observed
    • stroma between the mammary glands is hyperplastic
    • at 5 months two females develop bilateral swollen, lumpy thoracic mammary glands with abundant alveolar and ductal proliferation containing abundant secretions
    • at 5 months of age, female mice exhibit epithelial and stromal proliferation
    • the female founder mouse developed a mass during pregnancy that receded followed by development of masses in the inguinal fat pad and soft tissues of the upper thorax consisting of adenocarcinoma without metastasis
    • at 4 months of age, female mice develop numerous lumps within thoracic and inguinal areas of the mammary glands with large cystic spaces and abundant secretion within the lumen along with solid hyperplasias
    • female mice exhibit abnormal ductal trees
    • female mice exhibit cystically dilated alveoli
    • abnormal mammary gland growth during pregnancy (MGI Ref ID J:28453)
      • during pregnancy, female mice exhibit increased stromal cell proliferation, more prominent nuclei of epithelial cells, and production of more secretion than in wild-type mice
      • after 3 month, female mice that have been pregnant develop an inguineal mammary fat pad that develops into a circumscribed, firm tumor
      • during pregnancy, female mice exhibit abnormal mammary gland hyperplasia with cysts that are more prominent and secretions that are more inspissated than in wild-type mice
    • mammary gland alveolar hyperplasia (MGI Ref ID J:28453)
      • at day 90
    • mammary gland duct hyperplasia (MGI Ref ID J:28453)
      • at 5 months of age
    • mammary gland hyperplasia (MGI Ref ID J:71696)
      • female mice exhibit lobular development similar to a lactating wild-type mice except that the alveoli are irregular and dilated with interstitial stroma edema and a modest increase in leukocyte infiltration
      • however, nulliparous mice exhibit minimal lobular development and no stromal response
      • virgin females exhibit papillary hyperplasia
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(MMTVTGFA)29Rjc
Allele Name transgene insertion 29, Robert J Coffey
Allele Type Transgenic (random, expressed)
Mutation Made By Robert Coffey,   Vanderbilt University Medical Center
Strain of Origin(C57BL/6 x DBA/2)F2
Expressed Gene TGFA, transforming growth factor, alpha, human
Promoter MMTV, Mouse Mammary Tumor Virus, MMTV
Molecular Note This transgene contains the mouse mammary tumor virus LTR and the normal allele of the human transforming growth factor alpha gene. The vector also contains exons 2 and 3 of the rabbit beta-globin gene. Lines 254, 257, 64 and 29 were produced. [MGI Ref ID J:28453]
 
 

Genotyping

Genotyping Information

Genotyping Protocols

Tg(MMTVTGFA), Standard PCR
Tg(MMTVTGFA), Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References

Selected Reference(s)

Matsui Y; Halter SA; Holt JT; Hogan BL; Coffey RJ. 1990. Development of mammary hyperplasia and neoplasia in MMTV-TGF alpha transgenic mice. Cell 61(6):1147-55. [PubMed: 2161707]  [MGI Ref ID J:28453]

Additional References

Halter SA; Dempsey P; Matsui Y; Stokes MK; Graves-Deal R; Hogan BL; Coffey RJ. 1992. Distinctive patterns of hyperplasia in transgenic mice with mouse mammary tumor virus transforming growth factor-alpha. Characterization of mammary gland and skin proliferations. Am J Pathol 140(5):1131-46. [PubMed: 1316084]  [MGI Ref ID J:72085]

Muller WJ; Arteaga CL; Muthuswamy SK; Siegel PM; Webster MA; Cardiff RD; Meise KS; Li F; Halter SA; Coffey RJ. 1996. Synergistic interaction of the Neu proto-oncogene product and transforming growth factor alpha in the mammary epithelium of transgenic mice. Mol Cell Biol 16(10):5726-36. [PubMed: 8816486]  [MGI Ref ID J:35344]

Pierce DF Jr; Gorska AE; Chytil A; Meise KS; Page DL; Coffey RJ Jr; Moses HL. 1995. Mammary tumor suppression by transforming growth factor beta 1 transgene expression. Proc Natl Acad Sci U S A 92(10):4254-8. [PubMed: 7753792]  [MGI Ref ID J:71696]

Tg(MMTVTGFA)29Rjc related

Cardiff RD; Anver MR; Gusterson BA; Hennighausen L; Jensen RA; Merino MJ; Rehm S; Russo J; Tavassoli FA; Wakefield LM; Ward JM; Green JE. 2000. The mammary pathology of genetically engineered mice: the consensus report and recommendations from the Annapolis meeting [see comments] Oncogene 19(8):968-88. [PubMed: 10713680]  [MGI Ref ID J:61035]

Cardiff RD; Munn RJ. 1995. Comparative pathology of mammary tumorigenesis in transgenic mice. Cancer Lett 90(1):13-9. [PubMed: 7720037]  [MGI Ref ID J:72081]

Coffey RJ Jr; Meise KS; Matsui Y; Hogan BL; Dempsey PJ; Halter SA. 1994. Acceleration of mammary neoplasia in transforming growth factor alpha transgenic mice by 7,12-dimethylbenzanthracene. Cancer Res 54(7):1678-83. [PubMed: 8137281]  [MGI Ref ID J:72080]

Gorska AE; Jensen RA; Shyr Y; Aakre ME; Bhowmick NA; Moses HL. 2003. Transgenic mice expressing a dominant-negative mutant type II transforming growth factor-beta receptor exhibit impaired mammary development and enhanced mammary tumor formation. Am J Pathol 163(4):1539-49. [PubMed: 14507660]  [MGI Ref ID J:85799]

Halter SA; Dempsey P; Matsui Y; Stokes MK; Graves-Deal R; Hogan BL; Coffey RJ. 1992. Distinctive patterns of hyperplasia in transgenic mice with mouse mammary tumor virus transforming growth factor-alpha. Characterization of mammary gland and skin proliferations. Am J Pathol 140(5):1131-46. [PubMed: 1316084]  [MGI Ref ID J:72085]

Jatoi A; Cleary MP; Tee CM; Nguyen PL. 2001. Weight gain does not preclude increased ubiquitin conjugation in skeletal muscle: an exploratory study in tumor-bearing mice. Ann Nutr Metab 45(3):116-20. [PubMed: 11423703]  [MGI Ref ID J:70639]

Lenferink AE; Simpson JF; Shawver LK; Coffey RJ; Forbes JT; Arteaga CL. 2000. Blockade of the epidermal growth factor receptor tyrosine kinase suppresses tumorigenesis in MMTV/Neu + MMTV/TGF-alpha bigenic mice. Proc Natl Acad Sci U S A 97(17):9609-14. [PubMed: 10931950]  [MGI Ref ID J:64071]

Muller WJ; Arteaga CL; Muthuswamy SK; Siegel PM; Webster MA; Cardiff RD; Meise KS; Li F; Halter SA; Coffey RJ. 1996. Synergistic interaction of the Neu proto-oncogene product and transforming growth factor alpha in the mammary epithelium of transgenic mice. Mol Cell Biol 16(10):5726-36. [PubMed: 8816486]  [MGI Ref ID J:35344]

Norgaard P; Law B; Joseph H; Page DL; Shyr Y; Mays D; Pietenpol JA; Kohl NE; Oliff A; Coffey RJ Jr; Poulsen HS; Moses HL. 1999. Treatment with farnesyl-protein transferase inhibitor induces regression of mammary tumors in transforming growth factor (TGF) alpha and TGF alpha/neu transgenic mice by inhibition of mitogenic activity and induction of apoptosis. Clin Cancer Res 5(1):35-42. [PubMed: 9918200]  [MGI Ref ID J:52053]

Pierce DF Jr; Gorska AE; Chytil A; Meise KS; Page DL; Coffey RJ Jr; Moses HL. 1995. Mammary tumor suppression by transforming growth factor beta 1 transgene expression. Proc Natl Acad Sci U S A 92(10):4254-8. [PubMed: 7753792]  [MGI Ref ID J:71696]

Witty JP; Lempka T; Coffey RJ Jr; Matrisian LM. 1995. Decreased tumor formation in 7,12-dimethylbenzanthracene-treated stromelysin-1 transgenic mice is associated with alterations in mammary epithelial cell apoptosis. Cancer Res 55(7):1401-6. [PubMed: 7882342]  [MGI Ref ID J:56328]

Xie L; Xu BJ; Gorska AE; Shyr Y; Schwartz SA; Cheng N; Levy S; Bierie B; Caprioli RM; Moses HL. 2005. Genomic and proteomic analysis of mammary tumors arising in transgenic mice. J Proteome Res 4(6):2088-98. [PubMed: 16335954]  [MGI Ref ID J:106939]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

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
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
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
  • 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
 
  Considerations for Choosing Controls
  USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
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