B6.FVB-Tg(MMTV-PyVT)634Mul/LellJ

Stock number: 022974
Product name: MMTV-PyMT
Strain synonyms: MMTV-PyVmT, MT634, MTAG, PyMT, PyV-mT, PyVT
Research areas: Cancer Research

Description

MMTV-PyMT (MMTV-PyVmT) females develop palpable mammary tumors which metastasize to the lung. Mean latency is 92 days of age. Male carriers develop mammary tumors with a later onset. These mice express the Polyoma Virus middle T antigen under the direction of the mouse mammary tumor virus promoter/enhancer and may be suitable for use in studies related to breast cancer and altering the tumor microenvironment.

Detailed description

The MMTV-PyVmT transgene has the mouse mammary tumor virus (MMTV) long terminal repeat upstream of a cDNA sequence encoding the Polyoma Virus middle T antigen (PyVmT). Transgenic mice are viable, but show loss of lactational ability due to activation of the estrogen responsive transgene during pregnancy leading to tumorigenesis. Female carriers develop palpable mammary tumors with a mean latency of 92 days of age, as compared with 53 days in FVB/N-Tg(MMTV-PyVT)634Mul/J mice (Stock No. 002374). Adenocarcinomas arise in virgin and breeder females and occasionally in males, which are well-differentiated, multifocal and eventually involve the entire mammary fat pad. Tumor-bearing females have reduced lung metastasis compared to the 80-90% incidence found in FVB/N-Tg(MMTV-PyVT)634Mul/J mice. 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 may be used as a platform to alter the tumor microenvironment. On the FVB/N background, 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 was shown to significantly enhance the durability of tumor reduction.

 

 

Development

To derive the MMTV-PyVmT transgene, 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 and founder line #634 was established. The donating investigator reports that these mice were backcrossed to C57BL/6J mice for at least 10 generations (see SNP note). Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 3 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.

 

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.