FVB/N-Tg(MMTVneu)202Mul/J

Stock number: 002376
Research areas: Cancer Research

Description

The female mice of this strain represent a mouse model of mammary tumor in humans. These mice express unactivated neu (Erbb2) under the transcriptional control of the mouse mammary tumor virus promoter/enhancer. 50% tumor incidence was observed in both virgin and non-virgin females by 205 days of age (Guy CT, et al., 1992. Proc Natl Acad Sci USA)

Detailed description

Mice homozygous for the MMTVneu (rat) transgene are viable and fertile. There is no phenotypic effect in males. The transgene is expressed at low levels in normal mammary epithelium, salivary gland, and lung. Higher expression is detected in tumor tissue. Focal mammary tumors first appear at 4 months, with a median incidence of 205 days. Both virgin and breeder mice develop tumors. Tumors arise as foci in hyperplastic, dysplastic mammary glands. Seventy-two percent of tumor-bearing mice that live to 8 months or longer develop metastatic disease to the lung. The phenotype of MMTV/unactivated neu transgenic mice differs from that of the MMTV/activated neu produced by Phil Leder, in which multifocal tumors involving the entire mammary epithelium arise.

Allele

Symbol: Tg(MMTVneu)202Mul
Name: transgene insertion 202, William Muller
MGI accession ID: MGI:1930204
Generation method: Transgenic
Attributes: Inserted expressed sequence
Marker symbol: Tg(MMTVneu)202Mul
Marker name: transgene insertion 202, William Muller
Chromosome: UN
Strain of origin: FVB/N
Expressed genes: Erbb2,erb-b2 receptor tyrosine kinase 2,rat
Molecular note: This transgene has the wild-type form of the rat gene. The transgene consists of an MMTV promoter, an unactivated rat Erbb2 cDNA sequence, and SV40 polyadenylation and splicing signals. Transgene expression was detected in the mammary gland in 5 out of 6 transgenic lines as determined by RNase protection assay. Low levels of transgene transcript were also detected in the salivary gland, spleen, thymus, and lung.
General note: Multiple transgenic lines were produced, including 202, 169, 510, 721, and 732.

In mice carrying both this transgene and Tg(Trp53R172H)8512Jmr, mammary tumors are first observed after two rounds of pregnancy and lactation at 112 days; the median latency was 154 days. All mice developed mammary tumors before 200 days of age. The neoplasms are of high grade and growth fraction, indicated by variable nuclear and cytological morphology, anaplasia, aneuploidy, and higher rates of mitosis and apoptosis. Metastatic incidence was not reported.

In virgin mice carrying both this transgene and Tg(MMTVTGFA)29Rjc, the mammary trees show extensive lobuloalveolar development comparable to a normal FVB lactating mouse. The alveoli of the bitransgenic mice have a denser cell lining in the walls. Their mammary glands are characterized by epithelial hyperplasia and dysplasia with stromal inflammation. In virgin mice, mammary tumors first arise at about 100 days; the median latency is approximately 180 days. Tumors are multifocal and involve the entire mammary epithelium. Metastatic incidence was not reported.