Strain Name:

B6;D2-Tg(MMTVTGFB1)46Hlm/J

Stock Number:

002375

Availability:

Cryopreserved - Ready for recovery

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; Transgenic;
Additional information on Genetically Engineered and Mutant Mice.
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Specieslaboratory mouse
GenerationF?+4N1p
 
Donating Investigator Harold Moses,   Vanderbilt-Ingram Cancer Center

Description
Mice carrying the (MMTVTGFB1)46Hlm transgene are viable, fertile, and able to lactate through multiple litters. The transgene is expressed in mammary epithelium of 13-week virgin as well as lactating animals. Expression was localized to ductal epithelium. Expression in salivary gland was also detected. Ductal development was markedly inhibited in virgin transgenic mice by 13 weeks. The effect on lateral branching was more severe in homozygous mice carrying 4 copies of the transgene. Epithelial proliferation as measured by BrdU labeling index was markedly reduced. Mammary glands from pregnant and lactating mice showed fully developed lobules, although transgenic mice had fewer lobules. No mammary tumors were found in transgenic mice followed for over 300 days. Offspring of crosses between transgenic mice overexpressing TGFA (which develop mammary carcinoma) and the TGFB1 transgenic mice also were free of mammary carcinoma.

Control Information

  Control
   100006 B6D2F1/J (approximate)
 
  Considerations for Choosing Controls

Related Strains

Strains carrying   Tg(MMTVTGFB1)46Hlm allele
002933   FVB/NJ-Tg(MMTVTGFB1)46Hlm/J
View Strains carrying   Tg(MMTVTGFB1)46Hlm     (1 strain)

View Strains carrying other alleles of MMTV     (18 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms
      assigned by genotype

Tg(MMTVTGFB1)46Hlm/0

        involves: C57BL/6 * DBA/2
  • endocrine/exocrine gland phenotype
  • *normal* endocrine/exocrine gland phenotype (MGI Ref ID J:72128)
    • despite abnormal morphology, mice are still able to produce milk and normally nurse their young
    • abnormal mammary gland morphology (MGI Ref ID J:72128)
      • abnormal branching of the mammary ductal tree (MGI Ref ID J:72128)
        • mammary duct tree branching development is suppressed due to decreased proliferation of mammary epithelial cells
        • at week 13, lateral branching is virtually absent
        • multiparous mice exhibit reduced ductal branching compared to wild-type mice
      • abnormal mammary gland epithelium morphology (MGI Ref ID J:72128)
        • during lactation ductal and alveolar epithelial cells appear more flattened and somewhat atrophic compared to in wild-type mice
      • abnormal mammary gland lobule morphology (MGI Ref ID J:72128)
        • pregnant and lactating glands exhibit fewer lobules than in wild-type mice
  • tumorigenesis
  • *normal* tumorigenesis (MGI Ref ID J:72128)
    • unlike with overexpression of TGFA, mice do not exhibit mammary tumors
    • decreased incidence of chemically-induced tumors (MGI Ref ID J:71696)
      • mice exhibit fewer DMBA-induced tumors than similarly treated wild-type mice
  • reproductive system phenotype
  • abnormal mammary gland morphology (MGI Ref ID J:72128)
    • abnormal branching of the mammary ductal tree (MGI Ref ID J:72128)
      • mammary duct tree branching development is suppressed due to decreased proliferation of mammary epithelial cells
      • at week 13, lateral branching is virtually absent
      • multiparous mice exhibit reduced ductal branching compared to wild-type mice
    • abnormal mammary gland epithelium morphology (MGI Ref ID J:72128)
      • during lactation ductal and alveolar epithelial cells appear more flattened and somewhat atrophic compared to in wild-type mice
    • abnormal mammary gland lobule morphology (MGI Ref ID J:72128)
      • pregnant and lactating glands exhibit fewer lobules than in wild-type mice

Genes & Alleles

Gene & Allele Information

 
Allele Symbol Tg(MMTVTGFB1)46Hlm
Allele Name transgene insertion 46, Harold L Moses
Allele Type Transgenic (random, expressed)
Mutation Made By Harold Moses,   Vanderbilt-Ingram Cancer Center
Strain of Origin(C57BL/6 x DBA/2)F2
Expressed Gene TGFB1, transforming growth factor-beta 1, simian
The transforming growth factor beta family of polypeptides have a wide spectrum of biologic effects, including involvement in mammary gland development. Originally identified for their ability to induce anchorage-independent growth of non-transformed fibroblasts, they have been found to inhibit proliferation of many epithelial cell types. They have an overlapping pattern of expression in mammary epithelium during branching morphogenesis, and administration of exogenous TGFb family members inhibits ductal morphogenesis and causes the proliferating stem cell layer at end buds to disappear. They also cause an increase in connective tissue deposition in front of treated end buds. They do not inhibit alveolar morphogenesis during pregnancy (an effect seen in the CSF-1 deficient op/op mice). The role of TGbs in cancer is complex, and may involve suppression of immune surveillance and abrogation of estrogen dependency as evidenced by effects of exogenous treatment on nude mouse-- human breast cancer cell line xenograft models. TGFb1 is normally secreted in a latent form, which can be constitutively activated by site-directed mutagenesis of cysteines in the pro region of the prepro form.
Promoter MMTV, Mouse Mammary Tumor Virus, MMTV
Molecular Note This transgene contains the mouse mammary tumor virus promoter and a modified allele of simian transforming growth factor, beta 1. In this modified allele cystein codons at positions 223 and 225 were changed to serine codons (this generates an active form of TGFB1). The construct also contained exons 2 and 3 of the rabbit beta-globin gene. [MGI Ref ID J:72128]
 
 

Genotyping

Genotyping Information

Genotyping Protocols

Tg(MMTVTGFB1)46Hlm, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References

Selected Reference(s)

Pierce DF Jr; Johnson MD; Matsui Y; Robinson SD; Gold LI; Purchio AF; Daniel CW; Hogan BL; Moses HL. 1993. Inhibition of mammary duct development but not alveolar outgrowth during pregnancy in transgenic mice expressing active TGF-beta 1. Genes Dev 7(12A):2308-17. [PubMed: 8253379]  [MGI Ref ID J:72128]

Additional References

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(MMTVTGFB1)46Hlm related

Ewan KB; Oketch-Rabah HA; Ravani SA; Shyamala G; Moses HL; Barcellos-Hoff MH. 2005. Proliferation of Estrogen Receptor-{alpha}-Positive Mammary Epithelial Cells Is Restrained by Transforming Growth Factor-{beta}1 in Adult Mice. Am J Pathol 167(2):409-17. [PubMed: 16049327]  [MGI Ref ID J:99950]

Francis SM; Bergsied J; Isaac CE; Coschi CH; Martens AL; Hojilla CV; Chakrabarti S; Dimattia GE; Khoka R; Wang JY; Dick FA. 2009. A functional connection between pRB and transforming growth factor beta in growth inhibition and mammary gland development. Mol Cell Biol 29(16):4455-66. [PubMed: 19506017]  [MGI Ref ID J:151417]

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]

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
   100006 B6D2F1/J (approximate)
 
  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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