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Strain Name:

B6.Cg-Tg(MMTV-TGFBR2)7Hlm/J

Stock Number:

004997

Availability:

Repository-Cryopreserved

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General Terms and Conditions

Genes & Alleles   TGFB2;   MMTV;   Tg(MMTV-TGFBR2)7Hlm;

Product Information

Strain Details

Type JAX® GEMM® Strain - Congenic
Additional information on JAX® GEMM® Strains.
Type JAX® GEMM® Strain - Mutant Strain
Type JAX® GEMM® Strain - Transgenic
Specieslaboratory mouse
Donating Investigator Harold Moses,   Vanderbilt-Ingram Cancer Center

Strain Description
These transgenic mice express a truncated human transforming growth factor, beta receptor II under the direction of the mouse mammary tumor virus promoter. The truncated human transforming growth factor, beta receptor II has defective kinase activity. The transgene (mRNA) is detected at low levels in mammary gland tissue of 13-15 week old mice and at higher levels in mice aged 18 to 23 weeks, by Northern blot analysis. In situ hybridization shows expression is localized to mammary gland epithelial cells of terminal ducts and alveolar buds. At 20 weeks of age, virgin females develop mammary epithelial hyperplasia and increased secretion of beta casein protein, characteristic of early to mid-pregnancy. Mice homozygous for the transgenic insert are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Half of all homozygous females are unable to feed pups. This mutant mouse strain may be useful in studies examining the induction of hyperplasia in mammary epithelial tissue.

Strain Development
A transgenic construct containing sequence encoding a truncated human TGFBR2 gene under the direction of the mouse mammary tumor virus LTR promoter/enhancer, and exons 2 and 3 of the rabbit beta-globin gene was injected into B6DBAF2 fertilized eggs.

Related Disease (OMIM) Terms

Breast Cancer
Mammalian Phenotype Terms assigned by genotype

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

Tg(MMTV-TGFBR2)7Hlm/0

        involves: C57BL/6 * DBA
  • endocrine/exocrine gland phenotype
  • abnormal lactation (MGI Ref ID J:46432)
    • the milk protein beta-Casein is detectable in the alveolar buds of non-pregnant females
  • mammary alveolar hyperplasia (MGI Ref ID J:46432)
    • alveolar hyperplasia is evident in non-pregnant females while no alveolar structures are observed in non-pregnant wild-type mice
    • the alveolar-like buds fill in the spaces between the ductal structure of the mammary gland
    • the morphology of the mammary gland resembles the morphology found in pregnant wild-type mice at early to mid-gestation
    • the hyperplasia observed is less severe than observed in mice homozygous for the transgene
  • reproductive system phenotype
  • abnormal lactation (MGI Ref ID J:46432)
    • the milk protein beta-Casein is detectable in the alveolar buds of non-pregnant females
  • mammary alveolar hyperplasia (MGI Ref ID J:46432)
    • alveolar hyperplasia is evident in non-pregnant females while no alveolar structures are observed in non-pregnant wild-type mice
    • the alveolar-like buds fill in the spaces between the ductal structure of the mammary gland
    • the morphology of the mammary gland resembles the morphology found in pregnant wild-type mice at early to mid-gestation
    • the hyperplasia observed is less severe than observed in mice homozygous for the transgene

Tg(MMTV-TGFBR2)7Hlm/Tg(MMTV-TGFBR2)7Hlm

        involves: C57BL/6 * DBA
  • endocrine/exocrine gland phenotype
  • abnormal involution of the mammary gland (MGI Ref ID J:85799)
    • there is consistent retardation of involution observed in mice both 7 and 10 days after weaning compared to control mice
  • abnormal lactation (MGI Ref ID J:46432)
    • the milk protein beta-Casein is detectable in the alveolar buds of non-pregnant females
    • the concentration and location of the beta-Casein is similar to what is found in 12.5-day pregnant females
    • mice are frequently unable to feed their pups
    • while alveolar hyperplasia with some milk production occurs early in pregnancy (15 days), the mammary glands fail to develop into fully functional organs as indicated by less extensive alveolar development and decreased milk production compared to non-transgenic controls
  • abnormal mammary gland growth during lactation (MGI Ref ID J:85799)
    • there is accelerated development and differentiation of mammary epithelial cells during early to mid-pregnancy but impaired development during the last stages of pregnancy
  • mammary alveolar hyperplasia (MGI Ref ID J:46432)
    • alveolar hyperplasia is evident in non-pregnant females while no alveolar structures are observed in non-pregnant wild-type mice
    • the alveolar-like buds fill in the spaces between the ductal structure of the mammary gland
    • the morphology of the mammary gland resembles the morphology found in pregnant wild-type mice at early to mid-gestation
    • the hyperplasia observed is more severe than observed in mice hemizyguos for the transgene
    • mice 15 days into their first pregnancy have more prominent vacuoles in the alveoli than in control mice
    • the alveolar are also in a more differentiated state as indicated by the presence of milk proteins in the lumen
  • mammary gland hypoplasia (MGI Ref ID J:85799)
    • mice have fewer alveoli 1 day after the onset of lactation than do control mice
  • reproductive system phenotype
  • abnormal involution of the mammary gland (MGI Ref ID J:85799)
    • there is consistent retardation of involution observed in mice both 7 and 10 days after weaning compared to control mice
  • abnormal lactation (MGI Ref ID J:46432)
    • the milk protein beta-Casein is detectable in the alveolar buds of non-pregnant females
    • the concentration and location of the beta-Casein is similar to what is found in 12.5-day pregnant females
    • mice are frequently unable to feed their pups
    • while alveolar hyperplasia with some milk production occurs early in pregnancy (15 days), the mammary glands fail to develop into fully functional organs as indicated by less extensive alveolar development and decreased milk production compared to non-transgenic controls
  • abnormal mammary gland growth during lactation (MGI Ref ID J:85799)
    • there is accelerated development and differentiation of mammary epithelial cells during early to mid-pregnancy but impaired development during the last stages of pregnancy
  • mammary alveolar hyperplasia (MGI Ref ID J:46432)
    • alveolar hyperplasia is evident in non-pregnant females while no alveolar structures are observed in non-pregnant wild-type mice
    • the alveolar-like buds fill in the spaces between the ductal structure of the mammary gland
    • the morphology of the mammary gland resembles the morphology found in pregnant wild-type mice at early to mid-gestation
    • the hyperplasia observed is more severe than observed in mice hemizyguos for the transgene
    • mice 15 days into their first pregnancy have more prominent vacuoles in the alveoli than in control mice
    • the alveolar are also in a more differentiated state as indicated by the presence of milk proteins in the lumen
  • mammary gland hypoplasia (MGI Ref ID J:85799)
    • mice have fewer alveoli 1 day after the onset of lactation than do control mice
  • tumorigenesis
  • mammary adenocarcinoma (MGI Ref ID J:85799)
    • mice that have experienced two rounds of pregnancy have a frequency of spontaneous mammary carcinoma
    • 47% of these females develop mammary tumors with a median latency of 27.5 months
    • 72% of these tumors are high grade mammary intraepithelial neoplasias
    • the remaining 28% are invasive adenocarcinomas or adenosquamous carcinomas

Gene & Allele Details

Allele Symbol Tg(MMTV-TGFBR2)7Hlm
Allele Name transgene insertion 7, Harold L Moses
Common Name(s) MMTV-DNIIR-8;
Mutation Made By Agnieszka Gorska,   Vanderbilt Univ Schl of Medicine
Strain of Origin(C57BL/6 x DBA)F2
Expressed Gene TGFB2, transforming growth factor, beta 2, human
Promoter MMTV, Mouse Mammary Tumor Virus, MMTV
Molecular Note A human cDNA encoding a carboxy-terminally truncated TGFB2 was adjoined to an MMTV regulatory region. While the encoded receptor contains the complete extracellular and transmembrane domains and is therefore capable of ligand binding and and interacting with type 1 receptors, it lacks the kinase domain. Expression was driven in mammary epithelial cells by the MMTV LTR promoter/enhancer. Transgenic expression was verified by Northern blot analysis. [MGI Ref ID J:46432]

Control Information

   
   Wildtype mice from the colony or C57BL/6J mice (Stock No. 000664) may be used as controls.
 
  Considerations for Choosing Controls

Genotyping Protocols

Tg(MMTV-TGBR2)

Colony Maintenance

Breeding & HusbandryThe resulting transgenic mice were backcrossed for 20 generations on the C57BL/6 background. The strain is maintained as a homozygote. Surrogate mothers are used because 50% homozygous females cannot feed pups.

Related Strains

View Strains carrying other alleles of MMTV     (17 strains)

Research Applications

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

Cancer Research

References

Selected Reference(s)

Gorska AE; Joseph H; Derynck R; Moses HL; Serra R. 1998. Dominant-negative interference of the transforming growth factor beta type II receptor in mammary gland epithelium results in alveolar hyperplasia and differentiation in virgin mice. Cell Growth Differ 9(3):229-38. [PubMed: 9543389]  [MGI Ref ID J:46432]

Additional References

Price and Supply Information

Strain Name: B6.Cg-Tg(MMTV-TGFBR2)7Hlm/J
Stock Number: 004997

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 Cryopreserved Embryos
This strain is also available as cryopreserved embryos from our Repository. Orders for cryopreserved embryos are supplied subject to a signed agreement that must be returned to the Customer Service Department after order placement. 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 from our repository, please visit our Cryopreserved Embryos web page.
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.

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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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