FVB.Cg-Tg(MMTV-vHaras)SH1Led/J

Stock number: 004363
Product name: MMTV/v-Ha-ras
Research areas: Cancer Research

Description

These MMTV-v-Ha-ras mice express the Harvey RAS (human) gene and develop malignant lymphoid tissue and mammary and salivary gland tumors as early as 5 weeks of age.

Detailed description

These transgenic mice express the Harvey RAS (human) gene under the direction of the mouse mammary tumor virus promoter. The majority of expression of the transgene is detected in the mammary tissue and salivary glands. Both male and female transgenic mice develop malignant lymphoid tissue and mammary and salivary gland tumors as early as 5 weeks of age. Half of the female transgenic animals develop tumors by 6 months of age. Histological analysis of mammary tumors revealed most of the tumors were adenocarcinomas and were locally invasive with some cases of metastasis to liver and/or lung. The tumors were found to express the transgene transcript. Protein-tyrosine phosphatase epsilon mRNA and protein was found to be highly expressed only in mammary tumors. In 20% of the transgenic mice diffuse benign hyperplasia develops in the Harderian lacrimal gland causing bilateral exophthalmia. The donating investigator reports hemizygous females develop tumors by delivery of their first litter (i.e. tumorigenesis is accelerated by pregnancy); and hemizygous males develop large salivary gland tumors in the neck and eye opacity by 5 to 6 months of age. The donating investigator has found hemizygous males to have low sperm counts and high incidences of sperm abnormalities resulting in low fertility. This transgenic mouse strain represents a model that may be useful in studies of mammary carcinoma.

Development

A transgenic construct, pA9 chimeric plasmid, containing the p21 structural gene of Harvey murine sarcoma virus (Ha-MuSV) and the MMTV promoter was injected into fertilized B6;CD-1 mouse eggs. Transgenic mice were later backcrossed to FVB/N. The Donating Investigator reports that the mice were backcrossed to FVB/N for at least 10 generations before arriving at The Jackson Laboratory.

Allele

Symbol: Tg(MMTV-vHaras)SH1Led
Name: transgene insertion SH1, Philip Leder
MGI accession ID: MGI:2447530
Generation method: Transgenic
Attributes: Inserted expressed sequence
Marker symbol: Tg(MMTV-vHaras)SH1Led
Marker name: transgene insertion SH1, Philip Leder
Chromosome: UN
Strain of origin: (CD-1 x C57BL/6J)F1
Expressed genes: vHa-ras,Harvey rat sarcoma viral oncogene homolog,
Molecular note: This transgene contains the MMTV (mouse mammary tumor virus) promoter and an allele of the Harvey rat sarcoma viral oncogene (viral) carrying two activating point mutations: one in codon 12, Gly12Arg, and one in codon 59, Ala59Thr. The transgenic construct was reported to be highly expressed in the mammary glands and salivary glands, expressed in the Harderian glands, thymus and spleen, slightly expressed in the lungs, ovaries and kidneys, and little or no expression was reported to have been observed in the liver and skeletal muscle of these mice.
General note: Multiple transgenic lines were produced.

Both male and female transgenic mice develop malignant lymphoid tissue and mammary and salivary gland tumors as early as 5 weeks of age. Half of the female transgenic animals develop tumors by 6 months of age. Histological analysis of mammary tumors revealed most of the tumors were adenocarcinomas and were locally invasive with some cases of metastasis to liver and/or lung. The tumors were found to express the transgene transcript. Protein-tyrosine phosphatase epsilon mRNA and protein was found to be highly expressed only in mammary tumors. In 20% of the transgenic mice diffuse benign hyperplasia develops in the Harderian lacrimal gland causing bilateral exophthalmia. Hemizygous transgenic female mice develop tumors by delivery time of first litter with tumorigenesis accelerated by pregnancy. Hemizygous transgenic male mice develop large salivary gland tumors in the neck and eye opacity by 5 to 6 months of age. Hemizygous males have low sperm counts and high incidence of sperm abnormalities resulting in low fertility.