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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 Mutant Mice. Species laboratory mouse Donating Investigator 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 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 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 (18 strains)
View Mammalian Phenotype Terms
Mammalian Phenotype Terms
assigned by genotype
Tg(MMTV-Notch4)3Rnc/0
involves: FVB/N
- endocrine/exocrine gland phenotype
- abnormal gland morphology (MGI Ref ID J:11644)
- glands of the nasal mucosa and maxiallary sinus contain proliferating immature ductal cells and are incompletely differentiated
- abnormal Harderian gland morphology (MGI Ref ID J:11644)
- hyperplasia of immature ductal cells is seen frequently in the Harderian gland
- abnormal lacrimal gland morphology (MGI Ref ID J:11644)
- hyperplasia of immature ductal cells is seen frequently in the extraorbital lacrimal gland
- abnormal mammary gland morphology (MGI Ref ID J:11644)
- hyperplastic nodular lesions and multifocal neoplastic lesions at multiple sites in the fat pad of mammary glands
- mammary gland secretory lobules and alveoli are absent in parous females
- abnormal mammary gland development (MGI Ref ID J:11644)
- 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
- mammary gland alveolar and ductal structures are sparse
- in parous females, lobular-alveolar development is incomplete; secretory lobules and alveoli are largely missing
- mammary ductal hyperplasia (MGI Ref ID J:11644)
- abnormal salivary gland morphology (MGI Ref ID J:11644)
- major and minor salivary glands show severe ductular hyperplasia and incomplete differentiation
- proliferating ductules appear to consist of immature cell types
- abnormal parotid gland morphology (MGI Ref ID J:11644)
- hyperplastic lesions of the parotid salivary glands
- abnormal sublingual gland morphology (MGI Ref ID J:11644)
- hyperplastic lesions of the sublingual salivary glands
- occasionally observe serous metaplasia in the sublingual gland
- abnormal submandibular gland morphology (MGI Ref ID J:11644)
- hyperplastic lesions of the submandibular salivary glands
- abnormal lactation (MGI Ref ID J:11644)
- parous females fail to lactate
- tumorigenesis
- increased metastatic potential (MGI Ref ID J:11644)
- lung metastases in 4 of 7 mutants with mammary tumors
- mammary adenocarcinoma (MGI Ref ID J:11644)
- focal and often multiple poorly differentiated mammary adenocarcinomas appear in the majority of transgenics between 2 and 7 months of age
- salivary adenocarcinoma (MGI Ref ID J:11644)
- focal and often multiple poorly differentiated salivary adenocarcinomas appear in the majority of transgenics between 2 and 6 months of age
- reproductive system phenotype
- abnormal epididymis epithelium morphology (MGI Ref ID J:11644)
- the pseudostratified epithelium of the epididymis is disorganized
- abnormal lactation (MGI Ref ID J:11644)
- parous females fail to lactate
- abnormal mammary gland morphology (MGI Ref ID J:11644)
- hyperplastic nodular lesions and multifocal neoplastic lesions at multiple sites in the fat pad of mammary glands
- mammary gland secretory lobules and alveoli are absent in parous females
- abnormal mammary gland development (MGI Ref ID J:11644)
- 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
- mammary gland alveolar and ductal structures are sparse
- in parous females, lobular-alveolar development is incomplete; secretory lobules and alveoli are largely missing
- mammary ductal hyperplasia (MGI Ref ID J:11644)
- enlarged epididymis (MGI Ref ID J:11644)
- males exhibit severe epididymal hyperplasia
- male infertility (MGI Ref ID J:11644)
- oligozoospermia (MGI Ref ID J:11644)
- epididymis occasionally contains reduced sperm count
- digestive/alimentary phenotype
- abnormal salivary gland morphology (MGI Ref ID J:11644)
- major and minor salivary glands show severe ductular hyperplasia and incomplete differentiation
- proliferating ductules appear to consist of immature cell types
- abnormal parotid gland morphology (MGI Ref ID J:11644)
- hyperplastic lesions of the parotid salivary glands
- abnormal sublingual gland morphology (MGI Ref ID J:11644)
- hyperplastic lesions of the sublingual salivary glands
- occasionally observe serous metaplasia in the sublingual gland
- abnormal submandibular gland morphology (MGI Ref ID J:11644)
- hyperplastic lesions of the submandibular salivary glands
- vision/eye phenotype
- abnormal Harderian gland morphology (MGI Ref ID J:11644)
- hyperplasia of immature ductal cells is seen frequently in the Harderian gland
- abnormal lacrimal gland morphology (MGI Ref ID J:11644)
- hyperplasia of immature ductal cells is seen frequently in the extraorbital lacrimal gland
View Research Applications
Research Applications
This mouse can be used to support research in many areas including:
Notch4 relatedCancer Research
Increased Tumor Incidence (Adenomas)
Increased Tumor Incidence (Mammary Gland Tumors)
Increased Tumor Incidence (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
Cancer Research
Increased Tumor Incidence (Mammary Gland Tumors)
| 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 gene homolog 4 (Drosophila), 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, STD PCR, vers. 2
Helpful Links
Optimizing PCR Protocols
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]
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 |
|
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $1900.00
| Pricing for International shipping destinations |
|
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $2470.00
| Standard Supply | Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information. |
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| Supply Notes |
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| Control | ||
|---|---|---|
| Noncarrier | ||
| 001800 FVB/NJ | ||
| 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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