Site-specific rearrangements in the long terminal repeat of extra mouse mammary tumor proviruses in murine T-cell leukemias

Abstract

Extrac MMTV proviruses in T-cell leukemias of GR and C57/BL10 mice contain alterations in their long terminal repeat (LTR) sequence. The four different leukemias studied contain different deletions, but common hallmarks were observed around the recombination sites. At the 5′ end of the deletions we observed a common nonamer sequence, AGACAGGTG, in two leukemias and an almost identical sequence, AGAGCAGGTG, in two other leukemias. At the 3′ end of the deletions we invariably found a common stretch of five nucleotides, TTAAA. Three of the four leukemias showed nonconserved crossover sites. The deletions in two leukemias were replaced with neighboring sequences, generating direct repeats. The MMTV LTR characteristic open reading frame and glucocorticoid response element were altered in all four rearranged MMTV LTRs. These results demonstrate site specific rearrangements in the LTR of extra MMTV proviruses in T-cell leukemias and suggest that these rearrangements might permit expression of MMTV in a new target cell.