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Former Names FVB/N-TgN(MMTVInt3)3Rnc (Changed: 15-DEC-04 ) TgN(MMTVNotch4)3Rnc (Changed: 15-DEC-04 ) Type Mutant Strain; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation N?+6pN1p+N1p
Generation DefinitionsDonating Investigator Dr. Robert Callahan, National Institutes of Health Description
Male mice transgenic for the Notch4 gene (previously called Int3) are sterile, and females fail to lactate. Mammary tissue of females does not develop completely, exhibiting dramatic inhibition of alveolar-lobular development and reduced penetration of the mammary fat pad by ductal epithelium. Glandular epithelia of tissues expressing the activated form of Notch4 generally display severe ductal hyperplasia. Salivary glands fail to differentiate completely. Male transgenic mice exhibit severe epididymal hyperplasia, which is thought to be the cause of their sterility. Both male and female mice develop focal adenomas of the mammary and salivary glands.Development
Transgenic mice were generated using a 7.5 kb genomic DNA fragment containing the 3' portion of the mouse Notch4 gene under the influence of the Czech II MMTV LTR. FVB/N embryos were microinjected. The FF1 line was established by superovulating and mating the female founder to a nontransgenic FVB male, isolating single-cell embryos, and transferring them to a pseudopregnant CD1 mouse. Thereafter, mice newly born to subsequent FF1 Notch4 transgenic mice were routinely moved to foster mothers.
| Control | ||
|---|---|---|
| Noncarrier | ||
| 001800 FVB/NJ | ||
| Considerations for Choosing Controls | ||
Strains carrying other alleles of Notch4
010544 B6;129S1-Notch4tm1Grid/J View Strains carrying other alleles of Notch4 (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 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 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)
View Mammalian Phenotype Terms
Mammalian Phenotype Terms provided by MGI
assigned by genotype
Tg(MMTV-Notch4)3Rnc/0
involves: FVB/N
- endocrine/exocrine gland phenotype
- abnormal gland morphology
- glands of the nasal mucosa and maxiallary sinus contain proliferating immature ductal cells and are incompletely differentiated (MGI Ref ID J:11644)
- abnormal Harderian gland morphology
- hyperplasia of immature ductal cells is seen frequently in the Harderian gland (MGI Ref ID J:11644)
- abnormal mammary gland morphology
- abnormal mammary gland development
- inguinal mammary gland development is incomplete, with mutants showing a truncated version of the normal glandular penetration of the mammary fat pat and absence of end buds (MGI Ref ID J:11644)
- mammary gland alveolar and ductal structures are sparse (MGI Ref ID J:11644)
- in parous females, lobular-alveolar development is incomplete; secretory lobules and alveoli are largely missing (MGI Ref ID J:11644)
- mammary gland duct hyperplasia (MGI Ref ID J:11644)
- abnormal parotid gland morphology
- hyperplastic lesions of the parotid salivary glands (MGI Ref ID J:11644)
- abnormal salivary gland duct morphology
- abnormal sublingual gland morphology
- submandibular gland hyperplasia
- hyperplastic lesions of the submandibular salivary glands (MGI Ref ID J:11644)
- lactation failure
- parous females fail to lactate (MGI Ref ID J:11644)
- tumorigenesis
- increased metastatic potential
- lung metastases in 4 of 7 mutants with mammary tumors (MGI Ref ID J:11644)
- mammary adenocarcinoma
- focal and often multiple poorly differentiated mammary adenocarcinomas appear in the majority of transgenics between 2 and 7 months of age (MGI Ref ID J:11644)
- salivary adenocarcinoma
- focal and often multiple poorly differentiated salivary adenocarcinomas appear in the majority of transgenics between 2 and 6 months of age (MGI Ref ID J:11644)
- reproductive system phenotype
- abnormal epididymis epithelium morphology
- the pseudostratified epithelium of the epididymis is disorganized (MGI Ref ID J:11644)
- enlarged epididymis
- males exhibit severe epididymal hyperplasia (MGI Ref ID J:11644)
- male infertility (MGI Ref ID J:11644)
- oligozoospermia
- epididymis occasionally contains reduced sperm count (MGI Ref ID J:11644)
- digestive/alimentary phenotype
- abnormal parotid gland morphology
- hyperplastic lesions of the parotid salivary glands (MGI Ref ID J:11644)
- abnormal salivary gland duct morphology
- abnormal sublingual gland morphology
- submandibular gland hyperplasia
- hyperplastic lesions of the submandibular salivary glands (MGI Ref ID J:11644)
- vision/eye phenotype
- abnormal nasolacrimal duct morphology
- hyperplasia of immature ductal cells is seen frequently in the extraorbital lacrimal gland (MGI Ref ID J:11644)
- integument phenotype
- abnormal mammary gland morphology
- abnormal mammary gland development
- inguinal mammary gland development is incomplete, with mutants showing a truncated version of the normal glandular penetration of the mammary fat pat and absence of end buds (MGI Ref ID J:11644)
- mammary gland alveolar and ductal structures are sparse (MGI Ref ID J:11644)
- in parous females, lobular-alveolar development is incomplete; secretory lobules and alveoli are largely missing (MGI Ref ID J:11644)
- mammary gland duct hyperplasia (MGI Ref ID J:11644)
- lactation failure
- parous females fail to lactate (MGI Ref ID J:11644)
View Research Applications
Research Applications
This mouse can be used to support research in many areas including:
Cancer Research
Increased Tumor Incidence
Adenomas
Mammary Gland Tumors
Other Tissues/Organs
Endocrine Deficiency Research
Gonad Defects
Mammary Gland Defects
Reproductive Biology Research
Endocrine Deficiencies Affecting Gonads
Fertility Defects
Research Tools
Cancer Research
Endocrine Deficiency Research
Reproductive Biology Research
| Allele Symbol | Tg(MMTV-Notch4)3Rnc | ||
|---|---|---|---|
| Allele Name | transgene insertion 3, Robert Callahan | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | FF1 int-3; FVB-3; MMTV LTR-INT3; MMTV-int-3; TgN(MMTVInt3)3Rnc; | ||
| Strain of Origin | FVB/N | ||
| Expressed Gene | Notch4, notch 4, mouse, laboratory | ||
| Promoter | MMTV, Mouse Mammary Tumor Virus, MMTV | ||
| General Note | Six founder mice with similar phenotypes noted. One line established. | ||
| Molecular Note | A 7.5 kb genomic fragment derived from a Czech II mammary tumor was used to generate transgenic mice. The fragment contained MMTV envelope and 3' LTR sequences and a truncated portion of the mouse Notch4 gene. [MGI Ref ID J:11644] | ||
Genotyping Protocols
Tg(MMTV-Notch4)3Rnc, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
Jhappan C; Gallahan D; Stahle C; Chu E; Smith GH; Merlino G; Callahan R. 1992. Expression of an activated Notch-related int-3 transgene interferes with cell differentiation and induces neoplastic transformation in mammary and salivary glands. Genes Dev 6(3):345-55. [PubMed: 1372276] [MGI Ref ID J:11644]
Tg(MMTV-Notch4)3Rnc relatedSmith GH; Gallahan D; Diella F; Jhappan C; Merlino G; Callahan R. 1995. Constitutive expression of a truncated INT3 gene in mouse mammary epithelium impairs differentiation and functional development. Cell Growth Differ 6(5):563-77. [PubMed: 7544153] [MGI Ref ID J:26600]
Animal Health Reports
Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.Colony Maintenance
Breeding & Husbandry Hemizygous males are sterile, females can develop tumors as soon as six weeks. Hemizygous females do not lactate. Mating scheme:Tg/+ females to a +/+ males and foster every litter to a mother that lactates. Expected coat color from breeding:Albino
| Pricing for USA, Canada and Mexico shipping destinations |
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Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2250.00 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 on the strain data sheet for further information.
Supply Notes
- Cryorecovery - Standard.
Progeny testing is not required.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. 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. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 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).
| Pricing for International shipping destinations |
|
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2925.00 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 on the strain data sheet for further information.
Supply Notes
- Cryorecovery - Standard.
Progeny testing is not required.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. 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. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 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).
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Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
| Control | ||
|---|---|---|
| Noncarrier | ||
| 001800 FVB/NJ | ||
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
For Licensing and Use Restrictions view the link(s) below:
- Notice to customers in Canada.
| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
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