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Former Names FVB/N-TgN(WapInt3)10Rnc (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?+3F7pN1 Donating Investigator Robert Callahan, National Institutes of Health Appearance
albino
Related Genotype: Tyrc/TyrcDescription
In transgenic mice carrying the WAP/Int3 construct, mammary ductal growth was unaffected in virgin females, but growth and differentiation of secretory lobules during gestation was profoundly inhibited. Mammary dysplasia and tumorigenesis occurred in all breeding females by 25 weeks of age. In non-breeding WAP/Int3 females mammary tumor incidence also reached 100% but only after 70 weeks. The WAP/Int3 mammary tumors were highly malignant and most tumor-bearing females, irrespective of breeding history developed metastatic lung lesions. FVB/WAP/Int3 females are unable to lactate. This phenotype is different from that of the FVB-TgN(MMTVInt3)3Rnc strain mice. In virgin and multiparous mice of that strain, mammary ductal growth and secretory lobule development were both curtailed. Mammary adenocarcinomas are observed as early as 7 weeks, and salivary adenocarcinomas were also observed. Males were sterile. Differences in the phenotype are attributed to the tissue-specific promoters used. The WAP promoter directs expression of the transgene to the secretory epithelium, whereas the MMTV LTR is more widely expressed and at an earlier stage of mammary ductal development.
| Control | ||
|---|---|---|
| Noncarrier | ||
| 001800 FVB/NJ | ||
| Considerations for Choosing Controls | ||
Strains carrying other alleles of Wap
003552 B6129-Tg(Wap-cre)11738Mam/J 002409 B6;SJL-Tg(Wap-HRAS)69Lln Chr YSJL/J 003189 C57BL/6J-Tg(WAPTAg)3Knw/J 002500 C57BL/6J-Tg(WapIgf1)39Dlr/J 003188 C57BL/6J-Tg(WapTAg)1Knw 002410 FVB.Cg-Tg(Wap-HRAS)69Lln Chr YSJL/J 003078 FVB.Cg-Tg(WapIgf1)39Dlr/J 002678 FVB.Cg-Tg(WapTgfa)215Bri/J View Strains carrying other alleles of Wap (8 strains)
View Mammalian Phenotype Terms
Mammalian Phenotype Terms
assigned by genotype
Tg(WapNotch4)10Rnc/Y
involves: FVB/N
- endocrine/exocrine gland phenotype
- abnormal lactation (MGI Ref ID J:33193)
- parous females fail to lactate
- abnormal mammary gland growth during pregnancy (MGI Ref ID J:33193)
- gestating females exhibit abnormal development of secretory lobules such that during late pregnancy, lobular development is severely retarded, and no secretory activity is apparent in the glands
- pregnant and postpartum mammary glands show dysplastic ducts and poorly formed alveolar buds
- acini in day 1 postpartum lactating glands have small lumina, constricted by numerous nonpolar, undifferentiated epithelial cells, which contain little or no endoplasmic reticulum, secretory vesicles, or lipid droplets and no secretory particles are present in acinar lumina
- in ducts of postpartum females, the luminal epithelial cells appear condensed and moribund
- however, mammary ductal growth is unaffected in virgin females
- reproductive system phenotype
- abnormal lactation (MGI Ref ID J:33193)
- parous females fail to lactate
- abnormal mammary gland growth during pregnancy (MGI Ref ID J:33193)
- gestating females exhibit abnormal development of secretory lobules such that during late pregnancy, lobular development is severely retarded, and no secretory activity is apparent in the glands
- pregnant and postpartum mammary glands show dysplastic ducts and poorly formed alveolar buds
- acini in day 1 postpartum lactating glands have small lumina, constricted by numerous nonpolar, undifferentiated epithelial cells, which contain little or no endoplasmic reticulum, secretory vesicles, or lipid droplets and no secretory particles are present in acinar lumina
- in ducts of postpartum females, the luminal epithelial cells appear condensed and moribund
- however, mammary ductal growth is unaffected in virgin females
- tumorigenesis
- lung tumor (MGI Ref ID J:33193)
- most tumor-bearing females, irrespective of breeding history, develop metastatic lung tumors
- mammary adenocarcinoma (MGI Ref ID J:33193)
- all virgin and multiparous females develop mammary tumors, with a 50% incidence of tumors in virgins at 11 months of age and in breeding females at 5 months
Tg(WapNotch4)10Rnc/Y
involves: FVB/N
- tumorigenesis
- *normal* tumorigenesis (MGI Ref ID J:33193)
- males do not form mammary adenocarcinomas as are seen in females
| Allele Symbol | Tg(WapNotch4)10Rnc | ||
|---|---|---|---|
| Allele Name | transgene insertion 10, Robert Callahan | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | Tg(WapInt3)10Rnc; WAP/Int3; Wap-int3 tg; | ||
| Strain of Origin | FVB/N | ||
| Expressed Gene | Notch4, Notch homolog 4 (Drosophila), rat | ||
| Promoter | Wap, whey acidic protein, mouse, laboratory | ||
| Molecular Note | The transgene insert consisted of the mouse whey acidic acid promoter and the portion of the Notch4 gene encoding the intracellular domain. Wap promoter activity is restricted to the secretory mammary epithelial population. Four founder mice were identified. One line established from founder 10. Transmission analysis indicates that the transgene inserted into the X chromosome. [MGI Ref ID J:33193] | ||
Genotyping Protocols
Tg(WapNotch4)10Rnc, STD PCR, vers. 1
Helpful Links
Optimizing PCR Protocols
Gallahan D; Jhappan C; Robinson G; Hennighausen L; Sharp R; Kordon E; Callahan R; Merlino G; Smith GH. 1996. Expression of a truncated Int3 gene in developing secretory mammary epithelium specifically retards lobular differentiation resulting in tumorigenesis. Cancer Res 56(8):1775-85. [PubMed: 8620493] [MGI Ref ID J:33193]
Tg(WapNotch4)10Rnc relatedCardiff RD; Anver MR; Gusterson BA; Hennighausen L; Jensen RA; Merino MJ; Rehm S; Russo J; Tavassoli FA; Wakefield LM; Ward JM; Green JE. 2000. The mammary pathology of genetically engineered mice: the consensus report and recommendations from the Annapolis meeting [see comments] Oncogene 19(8):968-88. [PubMed: 10713680] [MGI Ref ID J:61035]
Raafat A; Zoltan-Jones A; Strizzi L; Bargo S; Kimura K; Salomon D; Callahan R. 2007. Kit and PDGFR-alpha activities are necessary for Notch4/Int3-induced tumorigenesis. Oncogene 26(5):662-72. [PubMed: 16878155] [MGI Ref ID J:117838]
Robinson GW; Wagner KU; Hennighausen L. 2001. Functional mammary gland development and oncogene-induced tumor formation are not affected by the absence of the retinoblastoma gene. Oncogene 20(48):7115-9. [PubMed: 11704837] [MGI Ref ID J:73006]
Colony Maintenance
Diet Information LabDiet® 5K52/5K67
| Pricing for USA, Canada and Mexico shipping destinations |
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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 |
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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. |
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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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| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
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