FVB/N-Tg(MMTV-PyVT)634Mul/J

Stock number: 002374
Product name: MMTV-PyMT
Research areas: Cancer Research

Description

Hemizygous MMTV-PyMT females develop palpable mammary tumors which metastasize to the lung.

These mice have high penetrance of early onset of mammary cancer compared to other mammary tumor models. Male carriers also develop mammary tumors with a later age of onset. MMTV-PyVT transgenic mice express the Polyoma Virus middle T antigen under the direction of the mouse mammary tumor virus promoter/enhancer.

This strain can be used as a platform to alter the tumor microenvironment.

Detailed description

The MMTV-PyVT transgene (MMTV-PyMT) includes the mouse mammary tumor virus (MMTV) long terminal repeat upstream of a cDNA sequence encoding the Polyoma Virus middle T antigen (PyVT). Transgenic mice are viable, but show loss of lactational ability coincident with transgene expression. Adenocarcinomas arise in virgin and breeder females as well as males. Tumors are multifocal, highly fibrotic, and involve the entire mammary fat pad. Males also develop adenocarcinoma of the seminal vesicles and hemangiomas. Female carriers develop palpable mammary tumors with a mean latency of 53 days of age, as compared with 92 days in B6.FVB-Tg(MMTV-PyVT)634Mul/LellJ mice (Stock No. 022974). Tumor-bearing females have 80-90% incidence of lung metastasis, a significant increase when compared to that found on the B6 congenic background. Transgene expression is detected at high levels in male and female mammary glands. Lower levels are detected in salivary gland, seminal vesicles, ovaries, and lungs (believed to be the result of pulmonary metastases) [Guy et al., 1992, Mol Cell Biol.].

This strain can be used as a platform to alter the tumor microenvironment. Tumor burden and pulmonary metastases have been shown to be reduced after in vivo TMP195 treatment by inducing the recruitment and differentiation of highly phagocytic and stimulatory macrophages within tumors. TMP195 treatment combined with chemotherapy regimens or T-cell checkpoint blockade in this model significantly enhances the durability of tumor reduction.

Of note, this transgene is also available on a congenic C57BL/6 genetic background as Stock No. 022974.

Development

To derive the MMTV-PyVT transgene (MMTV-PyMT), cDNA encoding the Polyoma Virus middle T antigen was inserted into the expression vector, pMMTV-SV40, resulting in a fusion gene of the PyVT oncogene and SV40 poly A and 3' processing signals, driven by the Mouse Mammary Tumor Virus (MMTV) LTR. Construct DNA was injected into the pronuclei of FVB/N zygotes. Transgenic progeny were identified by Southern blot analysis using a PyVT cDNA probe. Seven founder lines were established, and mice from founder line 634 were sent to The Jackson Laboratory. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize FVB/NJ oocytes (Stock No. 001800).

Allele

Symbol: Tg(MMTV-PyVT)634Mul
Name: transgene insertion 634, William Muller
MGI accession ID: MGI:2679595
Generation method: Transgenic
Attributes: Inserted expressed sequence
Marker symbol: Tg(MMTV-PyVT)634Mul
Marker name: transgene insertion 634, William Muller
Chromosome: UN
Strain of origin: FVB/N
Expressed genes: PyVT,Polyoma virus middle T antigen,polyoma virus
Molecular note: This transgene expresses polyoma virus middle T antigen under the control of the mouse mammary tumor virus LTR. Expression of this transgene was detected at high levels in male and female mammary glands. Other expression sites include salivary gland, seminal vesicles, ovaries, and lung.
General note: Additional lines produced include lines 121, 196, 235, 654, 668, 670.

These mice are used to study metastatic disease.