Faculty Research 1990 - 1999

Generation of a tumorigenic milk-borne mouse mammary tumor virus by recombination between endogenous and exogenous viruses.

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Animal, Base-Sequence, Female, Male, Mammary-Neoplasms-Experimental: et, Mammary-Tumor-Viruses-Mouse: ge, Mice, Mice-Inbred-AKR, Mice-Inbred-C57BL, Mice-Inbred-DBA, Milk, Molecular-Sequence-Data, Receptors-Antigen-T-Cell-alpha-beta: an, Recombination-Genetic, Repetitive-Sequences-Nucleic-Acid, Superantigens: ge, SUPPORT-NON-U-S-GOVT, SUPPORT-U-S-GOVT-P-H-S

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J Virol 1997 May;71(5):3895-903


CA45954/CA/NCI, CA52645/CA/NCI, CA65795/CA/NCI


Two novel exogenous mouse mammary tumor viruses (MMTV), BALB2 and BALB14, that encode superantigens (Sags) with Vbeta2+ and Vbeta14+ specificities, respectively, were found in the BALB/cT mouse strain. BALB/cT females were crossed with AKR/J males to generate F1 females. Foster nursing of BALB/cT mice on (BALB/cT x AKR/J)F1 mothers resulted in the generation of a new mouse strain, BALB/cLA, that had acquired a new exogenous MMTV (hereafter called LA) with a Vbeta6+/Vbeta8.1+-T-cell-specific Sag. Sequence analysis of the long terminal repeats of the BALB2, BALB14, and LA viruses indicated that LA virus resulted from recombination between BALB14 and the endogenous Mtv-7 provirus. Mtv-7 is expressed only in lymphoid tissues but not the mammary glands of Mtv-7-containing mouse strains such as AKR. In contrast, LA virus was highly expressed in the mammary gland, although it had the sag-specific region from Mtv-7. The LA virus, as well as different recombinant viruses expressed in the mammary glands of (BALB/cT x AKR/J)F1 mice, acquired a specific DNA sequence from BALB14 virus that is required for the mammary-gland-specific expression of MMTV. Since the Sag encoded by LA virus strongly stimulated cognate T cells in vivo, selection for recombinant virus with the Mtv-7 sag most likely occurred because the increased T-cell proliferation resulted in greater lymphoid and mammary gland cell infection. As a result of the higher virus titer, 80% of BALB/cLA females developed mammary gland tumors, although the incidence was only 40% in BALB/cT mice.

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