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Leukaemogenesis by the Mo + SV Moloney murine leukaemia virus (M-MuLV) variant in Eµ pim-1 transgenic mice: high frequency of recombination with a solo endogenous M-MuLV LTR in vivo

¹ Department of Molecular Biology and Biochemistry and Cancer Research Institute, University of California, Irvine, CA 92717, USA
and² Department of Pathology, Children's Hospital, Los Angeles, CA 90033, USA

We previously described an enhancer variant of Moloney murine leukaemia virus (M-MuLV), Mo + SV M-MuLV, in which the enhancers of MuLV have been deleted and replaced with the enhancers of the simian virus 40 (SV40). When this virus is injected into neonatal NIH Swiss mice, pre-B and B-lymphoblastic lymphomas develop with a latency of 17 months. Van Lohuizen et al. (1989) described a line of transgenic mice that carry an activated pim-1 proto-oncogene transgene (Eµ pim-1). They also reported that Eµ pim-1 transgenic mice show greatly accelerated lymphoma development when infected with wild-type M-MuLV at birth. In these experiments, neonatal Eµ pim-1 transgenic mice were infected intraperitoneally with Mo + SV M-MuLV. Marked acceleration of T-lymphoid leukaemia was seen. However, 10 of the 11 tumours analysed were found to be negative for the SV40 enhancers, but they still contained M-MuLV DNA as measured by Southern blot analysis. The LTRs on viruses cloned from two such tumours (as well as on virus recovered by infection onto NIH 3T3 cells) were characterized by PCR amplification, molecular cloning and sequence analysis. The LTR's from the two tumours were identical to each other and were distinct from both the Mo + SV M-MuLV and wild-type M-MuLV LTRs. However, they were identical to a rearranged solo M-MuLV LTR present in the Eµ pim-1 transgene. These results indicate that the recombination in vivo between Mo + SV M-MuLV and the Eµ pim-1 transgene yielded a replication-competent and pathogenic virus at high efficiency. This is the first report of in vivo recombination between an exogenous MuLV and a solo endogenous LTR.

^* Author for correspondence. Fax +1 714 824 4023. e-mail HYFAN@UCI.edu

Received 25 July 1994; accepted 23 September 1994.