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Mouse Retroviral Sequences Acquired by Cell Lines after Passaging through Nude Mice Detected by Hybridization of the fms Probe pSM3

National Institute of Environmental Health Sciences, Laboratory of Pulmonary Pathobiology, Research Triangle Park, North Carolina 27709 [C. W., P. N., J. C. B., M. J., T. G.], and Stratagene Cloning Systems, LaJolla, California 92037 [F. R. J., J. S.]

The expression of a large RNA transcript, 8.5 to 9.5 kilobases, possibly related to the fms oncogene in mouse, rat, and human tumor cells, has been described in the literature. However, the pSM3 fms probe used to detect this gene transcript contains a significant amount of the pol gene of the Susan McDonough strain of feline sarcoma virus from which it was derived. Using a fms probe which does not contain any viral pol sequences, no such "fms-related" transcripts were detected in cell lines previously reported to express the large transcripts. These cell lines did express a large 9.5-kilobase transcript which hybridized to a probe for murine leukemia virus. Partial sequence analysis of the 9.5-kilobase transcript detected with the pSM3 probe in transformed rat cells indicated sequence homology with AKV murine leukemia virus. Thus, the presence of large RNA transcripts, interpreted by us and others as being related to the oncogene fms, appears to be due to the expression of mouse retroviral sequences which hybridize to the viral pol region contained in the pSM3 fms probe. In the case of rat and human cells, such sequences appear to be acquired after the cells have been passaged in nude mice. These results should serve as a reminder of the important biohazard and data interpretation implications for investigations in which cells transfected with retroviral vector constructs are injected into nude mice, because rescue of the recombinant sequences in these cells could occur following infection by endogenous murine retroviral particles.

¹ To whom requests for reprints should be addressed.

Received 7/26/88. Revised 10/11/88. Accepted 10/28/88.