The relationship between alteration in the number of xenotropic virus-related sequences and non-H-2 histocompatibility (H) mutations in mice was investigated. Mutant classifications included gain, loss, and loss-gain mutations. Genomic DNA from a panel of non-H-2 H mutant strains on the C57BL/6 and BALB/c backgrounds was digested with a set of restriction enzymes with varying numbers of sites within endogenous xenotropic-related sequences. The digested DNA was then resolved on agarose gels. Southern blots of digested DNA were hybridized with the pXenv probe specific for the env sequence of xenotropic viral sequences. The number of hybridizing bands varied from 7 to 19, depending on the restriction enzyme and inbred background. Most mutant strains were identical in their restriction patterns to the respective background strains. However, two B6 mutant strains, KH84 and HZ54, differed from C57BL/6 at a single band which appeared to be inherited from BALB/c in the derivation of the two congenic strains. The HZ43 strain lacked a male-specific band shared by both C57BL/6 and BALB/c; this loss was evidently independent of the original mutation which was observed to be autosomal. However, the KH148B and KH84 strains on the C57BL/6 background lacked single B6 bands. Both mutants were classified as gain mutants. An examination of previous reciprocal graft rejection patterns and retrovirus linkage to non-H-2 H loci indicated a strong inverse relationship between a linked retroviral sequence and presentation of a non-H-2 H antigen. This inverse correlation is consistent with reports of gene inactivation following retroviral insertion.
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