Relationship in nucleic acid sequences between mouse mammary tumor virus variants.

Abstract

Primary cultures of mouse mammary carcinomas were used as a source of both radioactively labeled and unlabeled 60 Variants of the mouse mammary tumor virus (MMTV) have been identified by different biological characteristics such as virulence, host range, mode of transmission, and histological type of tumor induced (1-5). Proviral sequences of MMTV have been reported (6) to be uniformly omnipresent in the cellular genome of mouse strains with high and low mammary tumor incidence, and to be expressed in all tissues of mouse strains irrespective of their mammary tumor history (7). Those studies, however, were conducted with cDNA probes that did not represent the entire viral genome (6), and did not consider a possible difference in nucleic acid sequences between vertically and horizontally transmitted MMTVs. We report here, using the 60-70S RNAs of various MMTVs in competitive and direct hybridization studies, that the nucleic acid sequences of the horizontally transmitted MMTV variants from four mouse strains (RIII, C3H-AvY, GR, and A) are at least 95% homologous to one another, and are approximately 25% different from the vertically transmitted MMTV variant from the mouse strain C3H-AVYfB. No Isolation of Nucleic Acids. We isolated radioactively labeled 60-70S RNA from MMTVs as described previously (11,12). Unlabeled virus was purified by polyethylene glycol precipitation (12) and isopycnic sucrose centrifugation. RNA was extracted by use of the sodium dodecyl sulfate Pronase method followed by phenol extraction (11,12). Cellular DNA, isolated (13) and sheared by sonication resulted in DNA fragments with a sedimentation value of 6-8 S, as assayed by alkaline sucrose gradient sedimentation.Hybridization Conditions. A modification of the method used by Wright and Neiman (14) was used for molecular competition hybridizations. The hybridization mixtures, in 100 gl, contained 400 ,ug of cellular DNA fragments, 3H-or 32P-labeled 60-70S MMTV RNA as indicated, and increasing amounts of unlabeled RNA in hybridization mixture I [4 4635

Of mice, cats, and men: Is human breast cancer a Zoonosis?

“…Numerous transgenic mouse models have been developed (Li et al, 2000;Stewart et al, 1984), many of them utilizing MMTV-LTR for targeting transgene expression to the mammary epithelium and allowing stimulation by lactogenic hormones. In reproductively separated feral mouse species (Callahan et al, 1982Escot et al, 1986;Gallahan et al, 1986;Imai, 1996;Imai et al, 1994,;Morris et al, 1977;Schlom et al, 1978) and Asian mouse populations Michalides and Schlom, 1975;Teramoto et al, 1980), tumor formation occurs in low percentages. In certain Asian mouse populations of Mus musculus, BC occurs with less than 1% of incidence, and with relatively long latency, after 18 months of age.…”

Molecular Biological Characterization of a Highly Leukaemogenic Virus Isolated from the Mouse. III. Identity with Mouse Mammary Tumour Virus

“…The data of Fig. 2 (a) showed that DMBA-LV vRNA was able to protect MMTV (C3H) by 90~, indicating that the MMTV present in DMBA-LV is more related to milk-borne MMTV than to endogenous MMTV [the latter being only 70 to 75 related to milk-borne MMTV (Michalides & Schlom, 1975;Ringold et al, 1976)]. From the 1/2 Crt value (3.0 x 10 -2) the type B nucleotide sequences can be calculated to be present in at least a tenfold excess over the type C sequences.…”

Novel class of mouse mammary tumor virus-related DNA sequences found in all species of Mus, including mice lacking the virus proviral genome.

“…Most other inbred strains of mice have a low and variable incidence of mammary tumors which occur late in life. Yet, like the high-incidence strains, they carry in their germ line multiple copies of the MMTV proviral genome (3)(4)(5)(6). The extent to which the genetically transmitted MMTV proviral genomes are involved in the development of spontaneous mammary tumors in low-incidence mouse strains varies with the strain in question.…”