Molecular clones of endogenous murine leukemia virus-related DNA sequences from Balb/c mice: characterization of integration sites.

Eight recombinant DNA clones of endogenous murine leukemia virus (MuLV)-related DNA sequences have been isolated from a lambdaphage genomic library of Balb/c mouse DNA. Each clone contains LTR (long terminal repeat) and gag-related sequences, as well as 5' cellular DNA sequences. The virus-related sequences in each clone show an organization similar to that of integrated proviruses; those clones with the greatest length of MuLV-related sequences also contain pol and env gene-related sequences. One clone appears to contain an intact endogenous provirus. Unique cellular DNA segments from three of these clones were subcloned and used as specific "integration site" hybridization probes. Restriction fragment-length polymorphisms (RFLPs) were observed for these integration sites in the DNA of a number of different inbred mouse strains. One provirus-containing fragment was observed only in Balb/c mice while two others were observed in some but not all of the inbred mouse strains tested. Further restriction enzyme mapping of these three loci in the genomic DNA of Balb/c and C3H/HeJ or C57BL/6 mice indicated that the observed RFLPs were due to the presence of proviral DNA sequences in the Balb/c strain at these three integration sites which were lacking in the other mouse strains. The strain distribution of these three provirus insertions suggests that the BE 1 and 7 proviruses were widely, although not universally, present among the progenitors of modern inbred mouse strains, while the BE 16 provirus may be a recent addition to the genome of Balb/c mice.