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Type Mutant Stock; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation F?+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 | ||
|---|---|---|
| 100006 B6D2F1/J | (approximate) | |
| Considerations for Choosing Controls | ||
Strains carrying Tg(MMTVTGFB1)46Hlm allele
002933 FVB/NJ-Tg(MMTVTGFB1)46Hlm/J View Strains carrying Tg(MMTVTGFB1)46Hlm (1 strain)
Strains carrying other alleles of MMTV
004997 B6.Cg-Tg(MMTV-TGFBR2)7Hlm/J 002618 B6.Cg-Tg(MMTVtTA)1Mam/J 007962 B6.FVB-Tg(MMTV-neu/OT-I/OT-II)CBnel Tg(Trp53R172H)8512Jmr/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 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 (18 strains)
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
| 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 Protocols
Tg(MMTVTGFB1)46Hlm, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
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]
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 relatedEwan 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]
Colony Maintenance
Diet Information LabDiet® 5K52/5K67
| Pricing for USA, Canada and Mexico shipping destinations |
|
Animals Provided
Price (US dollars $) Cryorecovery Fee $1900.00 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.
| Pricing for International shipping destinations |
|
Animals Provided
Price (US dollars $) Cryorecovery Fee $2470.00 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.
| Standard Supply | Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information. |
|---|---|
| Supply Notes |
|
| 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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| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
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