A biochemical approach to the study of the transmission of mouse mammary tumor viruses in mouse strains RIII and C3H

Michalides, Rob; Vlahakis, George; Schlom, Jeffrey

doi:10.1002/ijc.2910180114

Cited by 48 publications

(37 citation statements)

References 23 publications

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“…3). Livers were used because the genomes of these cells contain only the proviral sequences of the endogenous MTV under these hybridization conditions (4,13 (Table 2). The mammary glands of the GR mouse at first lactation contained 143-fold more MTV RNA than did those of the B10 mouse and-9-fold more MTV RNA than those of the GR-Mtv-2-mouse.…”

Section: Methodsmentioning

confidence: 99%

“…It is not clear from the curves in Figs. 4 The association between these remaining MTV DNA sequences and late-appearing mammary tumors remains uncertain, because no spontaneous mammary tumors have been detected in the GR-Mtv-2-mice up to the age of 14 months (6). Other biological studies (17,18) also suggest that more than one Mtv gene is involved in mammary tumorigenesis in the GR mouse strain.…”

Section: Methodsmentioning

confidence: 99%

“…(i) Approximately four copies are present in the DNA of all mouse strains studied so far (4). (Ui) Eight extra copies are present in the DNA of only the GR mouse and these copies are associated with the Mtv-2 gene.…”

Section: Methodsmentioning

confidence: 99%

“…Mammary tumors that appear as a result of the infection of mammary gland cells by this exogenous MTV carry additional MTV proviral sequences in their DNA as a result of such an infection (4).…”

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Identification of the Mtv -2 gene responsible for the early appearance of mammary tumors in the GR mouse by nucleic acid hybridization

Deemter¹,

Nusse²,

Nie³

1978

Proc. Natl. Acad. Sci. U.S.A.

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In the mouse strain GR, the Mtv-2 gene controls the expression of large amounts of mammary tumor virus (MTV) antigens in the milk at first lactation. It also controls the early appearance of mammary tumors. We have investigated the number of MTV proviral sequences associated with this gene by nucleic acid hybridization between MTV [3H]cDNA and DNA from GR, BiO, and GR-Mtv-2-mice. BIO and GRMtv-2-mice lack Mtv-2 gene expression. The molecular hybridizations revealed that the DNA of GR mice contains 12 copies of MTV proviral sequences, whereas only 4 copies are present in the DNA of BlO and GR-Mtv-2-mice. We therefore conclude that the Mtv-2 gene in the GR mouse strain is associated with eight additional MTV proviral sequences. The four Mtv proviral sequences in the GR-Mtv-2-DNA might represent another MN gene in the GR mouse. Different amounts of MTV RNA are detected in mammary glands at first lactation of BiO and GR-Mtv-2-mice, even though both contain four copies of MTV proviral sequences. This indicates a difference between these two mouse strains either in the regulation of expression of these MTV proviral sequences or in the location of these sequences in the murine genome. Mtv-1 gene is linked to the presence of very low amounts of MTV antigens in the milk of the first lactation and to the appearance of mammary tumors in this strain relatively late in life (average, 13 months). In the GR mouse strain, another dominant gene, Mtv-2, controls the expression of large amounts of MTV antigens in the milk of the first lactation and the early appearance of mammary tumors (all before age 13 months), (3). It furthermore has been shown (4) that the numbers of MTV proviral copies in the genomes of the GR and C3Hf mouse strains are different. The DNA of C3Hf mice contained 3 or 4 MTV proviral copies per haploid genome, whereas the GR genome contained approximately 16 copies.The present study focuses on the relationship between the number of MTV proviral sequences in the cellular genome of GR mice and the Mtv-2 gene. Therefore a comparison was made between the number of MTV proviral copies in the DNA of somatic (liver) cells in mouse strains GR, C57BL, and a GR mouse lacking the Mtv-2 gene (GR-Mtv-2-). The GR-Mtv-2-strain was developed by introducing genetic material of the C57BL mouse into the GR mouse strain as described by v. Nie et al. (6). We report here that the Mtv-2 gene is associated with approximately eight MTV proviral copies per haploid genome, and that the GR mouse strain carries four additional MTV proviral sequences that are probably similar to another Mtv gene. The effect of different numbers of MTV proviral sequences on the expression of MTV RNA is discussed. MATERIALS AND METHODSViruses. The propagation and purification of the MTV virus of the Mm 5mt/cl cell line have been described (7). Rauscher leukemia virus was obtained from plasma of BALB/c mice infected with Rauscher leukemia virus. The virus was purified by equilibrium centrifugation in sucrose. Mice: GRS/A (GR) and C57BL/10 JA (B10) mi...

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Identification of the Mtv -2 gene responsible for the early appearance of mammary tumors in the GR mouse by nucleic acid hybridization

Deemter¹,

Nusse²,

Nie³

1978

Proc. Natl. Acad. Sci. U.S.A.

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“…For example, MMTV has been shown to be a natural etiologic agent of mammary tumors in M. musculus (26,27). By contrast, an endogenous type B virus isolated from guinea pigs is associated with a high incidence of leukemia rather than mammary adenocarcinoma (28,29). The ability of the M432 virus to productively infect tissue culture cell lines and presumably animals of murine species other than M. cervwcolor should facilitate a better understanding of its potential pathogenicity as well as the genetic and physiologic elements that control its infection and expression.…”

Section: Methodsmentioning

confidence: 99%

A new class of genetically transmitted retravirus isolated from Mus cervicolor.

Callahan¹,

Benveniste²,

Sherr³

et al. 1976

Proc. Natl. Acad. Sci. U.S.A.

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Electron Microscopy. Tissues and cell pellets were fixed in 2.5% glutaraldehyde, rinsed with several changes of 0.01 M phosphate-buffered saline, treated with Dalton's chromeosmium, and rinsed again with several changes of distilled, deionized water (6). The specimens were stained overnight with 1% uranyl-acetate in 50% ethanol, dehydrated with increasing concentrations of ethanol, followed by propylene oxide, and embedded in Luft Epon. Thin sections were stained with lead citrate. Negative stains were prepared by mixing isopycnically banded virus in 0.05 M sodium citrate (pH 6.0) with 2% potassium phosphotungstate (pH 4.0). The mixture was deposited on a carbon-coated grid, drained, and air-dried just prior to use. Viral Polymerase Assays. Virus from culture supernatants was concentrated and assayed for viral reverse transcriptase as described (2, 3). Reactions were carried out in a total volume of 0.1 ml using 0.5 Ml of virus (10 Mig of protein) and contained 50 mM Tris-HCI (pH 7.8), 4 mM dithiothreitol, 60 mM KCI, 0.03% Triton X-100, and MnCl2 or MgCl2 as indicated. Po-

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Differences in mouse mammary tumor viruses:Relationship to early and late occurring mammary tumors

Schlom¹,

Colcher²,

Drohan³

et al. 1977

Cancer

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The murine model has been used extensively to study the various factors involved in the etiology of mammary carcinoma. Inbred mouse strains have been classically categorized into (i) high incidence stains with tumors occurring relatively early in the life of the animal, or (ii) low or moderate incidence strains with tumors occurring later on in life. We have radioactively labeled the RNA genome of the mouse mammary tumor virus (MMTV) from each of several mouse strains. We report here, using the technique of molecular hybridization, that the class of MMTVs responsible for the early occurring mammary tumors in high incidence strains can be clearly distinguished from the MMTVs associated with late occurring mammary tumors in low or moderate incidence strains; we also demonstrate that minor differences in MMTV genomes can also exist within these classes. O u r findings show that MMTVs are transmitted via the germ line (as a germinal provirus) in some mouse strains, whereas in other strains, a non-germ line transmission is clearly demonstrated. Biochemical techniques can thus be used to track the mode of transmission of oncogenic viruses. The relationship of these findings to an understanding of the etiology of mammary carcinoma is discussed.

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A biochemical approach to the study of the transmission of mouse mammary tumor viruses in mouse strains RIII and C3H

Cited by 48 publications

References 23 publications

Identification of the Mtv -2 gene responsible for the early appearance of mammary tumors in the GR mouse by nucleic acid hybridization

Identification of the Mtv -2 gene responsible for the early appearance of mammary tumors in the GR mouse by nucleic acid hybridization

A new class of genetically transmitted retravirus isolated from Mus cervicolor.

Differences in mouse mammary tumor viruses:Relationship to early and late occurring mammary tumors

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