FVB/N-Tg(WapNotch4)10Rnc/J

Stock number: 002755
Research areas: Cancer Research

Description

WapNotch4 transgenic mice have the murine whey acidic protein (Wap) promoter fused to a portion of the Notch4 gene encoding the intracellular domain. These mice may be useful when studying mammary gland development and mouse mammary tumor onset.

Detailed description

The WapNotch4 transgene was designed with the murine whey acidic protein (Wap) promoter fused to a portion of the Notch 4 gene encoding the intracellular domain. This transgene integrated into the X Chromosome. Hemizygotes are viable and fertile, but FVB/WapNotch4 females are unable to lactate. In transgenic mice carrying the WapNotch4 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 WapNotch4 females mammary tumor incidence reached 100% but only after 70 weeks. The WapNotch4 mammary tumors were highly malignant and most tumor-bearing females, irrespective of breeding history developed metastatic lung lesions. This phenotype is different from that of FVB-TgN(MMTV-Int3)3Rnc mice (Stock No. 002437). In virgin and multiparous MMTV-Int3 mice, 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. Also, male MMTV-Int3 mice are 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.

Development

The WapNotch4 transgene was designed with the murine whey acidic protein (Wap) promoter fused to a portion of the Notch4 gene encoding the intracellular domain. The transgene was microinjected into fertilized FVB/N oocytes, and founder mice were bred to FVB/N mice. Mice from founder line 10, in which the transgene had inserted itself on the X chromosome, were maintained. Upon arrival at The Jackson Laboratory, transgenic mice were bred to FVB/NJ inbred mice (Stock No. 001800) to establish the colony.

Allele

Symbol: Tg(WapNotch4)10Rnc
Name: transgene insertion 10, Robert Callahan
MGI accession ID: MGI:1930202
Generation method: Transgenic
Attributes: Inserted expressed sequence
Marker symbol: Tg(WapNotch4)10Rnc
Marker name: transgene insertion 10, Robert Callahan
Chromosome: X
Strain of origin: FVB/N
Expressed genes: Notch4,notch 4,rat
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.