AKV MURINE LEUKEMIA-VIRUS ENHANCES BONE TUMORIGENESIS IN HMT-C-FOS-LTR TRANSGENIC MICE

hMt-c-fos-LTR transgenic mice (U. Ruther, D. Komitowski, F. R. Schuber t, and E. F. Wagner. Oncogene 4, 861-865, 1989) developed bone sarcoma s in 20% (3/15) of females at 448 +/- 25 days and in 8% (1/12) of male s at 523 days. After infection of newborns with Akv, an infectious ret rovirus derived from the ecotropic provirus of the AKR mouse, 69% (20/ 28) of female animals and 83% (24/29) of males developed malignant fib rous-osseous tumors. The tumors in infected transgenics developed with higher frequency and a 200-days shorter mean tumor latency period. Th e hMt-c-fos-LTR transgene was expressed in all the fibrous-osseous tum ors. They also showed newly integrated Akv proviruses, but in most tum ors Akv was detected and expressed in only a small number of the tumor cells. Wild-type C3H mice infected with Akv developed benign osteomas with an incidence of 33% and a latency period of 474 days. The data i ndicate that Akv exerts distinct pathogenic effects on the skeleton. I n hMt-c-fos-LTR transgenic mice, predisposed to bone sarcomagenesis, A kv acts synergistically with the fos transgene, resulting in the devel opment of fibrous-osseous tumors. (C) 1995 Academic Press, Inc.