Ecotropic murine leukemia virus DNA content of normal and lymphomatous tissues of BXH-2 recombinant inbred mice.

BXH-2 recombinant inbred mice spontaneously produce a B-tropic murine leukemia virus (MuLV) beginning early in life and have a high incidence of non-T-cell lymphomas. These traits are not characteristic of the progenitor strains (C57BL/6J and C3H/HeJ) or of 11 other BXH recombinant inbred strains. Since B-tropic virus expression may be causally related to the high incidence of lymphoma in this strain, we have analyzed the ecotropic MuLV DNA content of both normal and lymphomatous tissues of BXH-2 mice. Southern analysis and hybridization with an ecotropic MuLV DNA-specific probe showed that DNA of normal BXH-2 tissues contained both parental N-tropic MuLV proviruses but lacked endogenous B-tropic MuLV DNA sequences. In addition, none of 116 F1 hybrid mice derived from male BXH-2 mice spontaneously produced ecotropic MuLV early in life. These results suggest that the B-tropic virus is horizontally transmitted in BXH-2 mice. Southern analysis of DNA from tumor tissues of 12 BXH-2 mice showed that amplification of ecotropic-specific DNA sequences had occurred in lymphomatous tissues of 3 mice and suggested that these tumors were monoclonal. The number of newly acquired proviruses, which appeared to be structurally nondefective and integrated at different sites, varied from one to three copies. Since lymphomatous tissues from only 3 of 12 mice examined carried additional detectable ecotropic proviruses, these results suggest that amplification of ecotropic MuLV DNA sequences is not required for maintenance of transformation in BXH-2 lymphomas.