Molecular Cloning and Sequencing of the MTV-1 LTR: Evidence for a LTR Sequence Alteration

The vertically transmitted Mtv-1 provirus is the primary causative factor of mammary neoplasia in certain C3Hf strains that lack the horizontally transmitted mouse mammary tumor virus (MMTV). The studies here report the molecular cloning of the germ line 4.5 kb Mtv-1 3' EcoRI fragment and sequencing of the 3' Mtv-1 LTR. The Mtv-1 LTR sequence is closely related to the 5' Mtv-11 LTR sequence also reported here, as well as to known Mtv-8 and MMTV LTR sequences in the portion of MMTV and Mtv-8 LTRs previously demonstrated to contain transcriptional regulatory sequences. A 91 bp unique sequence region, Mtv-1 bp 862 to 952, exists in the Mtv-1 LTR, which is upstream of the sequence homology with the MMTV transcriptional regulatory domain. The Mtv-1 unique sequence region is distinct from a 117 bp sequence, bp 862 to 978, in the Mtv-11 LTR sequence as well as reported Mtv-8 and MMTV LTR sequences, and is present in the germ line Mtv-1 5' and 3' LTR-containing restriction fragments. S1 nuclease mapping experiments of C3Hf/Se mammary tumor poly(A) RNA with the cloned Mtv-1 and Mtv-11 LTRs exhibited a specific set of S1 protected fragments demonstrating that Mtv transcripts which accumulate in C3Hf spontaneous mammary tumors are encoded by the Mtv-1 provirus.