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 Congenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Generation ?+N1p (30-JAN-05)   Donating Investigator Harold Moses,   Vanderbilt-Ingram Cancer Center

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.

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.

Control Information

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

Related Strains

Strains carrying other alleles of MMTV

002618	B6.Cg-Tg(MMTVtTA)1Mam/J
007962	B6.FVB-Tg(MMTV-neu/OT-I/OT-II)CBnel Tg(Trp53R172H)8512Jmr/J
002375	B6;D2-Tg(MMTVTGFB1)46Hlm/J
010576	B6;SJL-Tg(MMTV-rtTA)4-1Jek/J
002459	B6D2-Tg(MMTVTGFA)254Rjc/J
002373	B6D2-Tg(MMTVTGFA)29Rjc/J
002870	B6SJL-Tg(Wnt1)1Hev/J
005038	FVB-Tg(MMTV-Erbb2)NK1Mul/J
004363	FVB.Cg-Tg(MMTV-vHaras)SH1Led/J
002953	FVB.Cg-Tg(MMTVTGFA)254Rjc/J
002934	FVB.Cg-Tg(Wnt1)1Hev/J
002437	FVB/N-Tg(MMTV-Notch4)3Rnc/J
002374	FVB/N-Tg(MMTV-PyVT)634Mul/J
002376	FVB/N-Tg(MMTVneu)202Mul/J
002933	FVB/NJ-Tg(MMTVTGFB1)46Hlm/J
003690	STOCK Tg(MMTV-Cdc37)1Stp/J
003337	STOCK Tg(MMTV-PIP)1Shu/J
003551	STOCK Tg(MMTV-cre)1Mam/J
003553	STOCK Tg(MMTV-cre)4Mam/J

View Strains carrying other alleles of MMTV     (19 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

Breast Cancer -

View Mammalian Phenotype Terms

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 gland 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 gland 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 gland 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 gland 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

View Research Applications

Research Applications

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

Cancer Research

Genes & Alleles

Gene & Allele Information

Allele Symbol		Tg(MMTV-TGFBR2)7Hlm
Allele Name		transgene insertion 7, Harold L Moses
Allele Type		Transgenic (random, expressed)
Common Name(s)		MMTV-DNIIR-7;
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 TGFBR2 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 interactingwith 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]

Genotyping

Genotyping Information

Genotyping Protocols

Tg(MMTV-TGFBR2)7Hlm, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

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

Tg(MMTV-TGFBR2)7Hlm related

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]

Health & husbandry

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.

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	The 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.

Purchasing information

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

Pricing

Supply Details

Standard Supply

Cryopreserved. 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.

Control Information

		Wildtype mice from the colony or C57BL/6J mice (Stock No. 000664) may be used as controls.
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's Genotype Promise

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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