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Strain Name:

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

Stock Number:

002375

Availability:

Repository-Cryopreserved


General Terms and Conditions

Genes & Alleles   TGFB1;   MMTV;   Tg(MMTVTGFB1)46Hlm;


Product Information

Strain Details

Type JAX® GEMM® Strain - Mutant Stock
Additional information on JAX® GEMM® Strains.
Type JAX® GEMM® Strain - Transgenic
Specieslaboratory mouse
Donating Investigator Harold Moses,   Vanderbilt-Ingram Cancer Center
GenerationF?+4N1p

Strain 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.

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)
      • pregnant and lactating glands exhibit fewer lobules than in wild type mice
      • during lactation ductal and alveolar epithelial cells appear more flattened and somewhat atrophic compared to in wild type mice
      • 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
  • tumorigenesis
  • *normal* tumorigenesis (MGI Ref ID J:72128)
    • unlike over expression 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)
    • pregnant and lactating glands exhibit fewer lobules than in wild type mice
    • during lactation ductal and alveolar epithelial cells appear more flattened and somewhat atrophic compared to in wild type mice
    • 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

Gene & Allele Details

Allele Symbol Tg(MMTVTGFB1)46Hlm
Allele Name transgene insertion 46, Harold L Moses
Mutation Made By Harold Moses,   Vanderbilt-Ingram Cancer Center
Strain of OriginB6D2F2
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]

Control Information

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

Genotyping Protocols

Tg(MMTVTGFB1)46Hlm

Colony Maintenance

Diet Information LabDiet® 5K52/5K67

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     (16 strains)

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

Price and Supply Information

Strain Name: B6;D2-Tg(MMTVTGFB1)46Hlm/J
Stock Number: 002375

Price Details

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Supply Details

Standard SupplyRepository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.
Supply Notes Cryorecovery - Standard.
The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery.

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; Email: jaxservices@jax.org.
This strain is included in the Induced Mutant Resource Colony collection.
Genomic DNA is available for this strain from the Mouse DNA Resource.

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Control InformationView Control Information in Strain Details.

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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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