Erythroid defects and increased retrovirally-induced tumor formation in Evi1 transgenic mice

Aberrant expression of the Evil (ecotropic virus integration site 1) proto- oncogene has been associated with hematopoietic malignancies in both mice a nd man. To determine the effect of enforced expression of Evil in vivo, we developed a transgenic mouse model utilizing the murine Sca-1 (Ly-6E.1) pro moter. Here, we describe the generation and analysis of three independent l ines of Evil transgenic mice. Transgenic animals of two founder lines devel oped normally. These mice did not show any obvious hematological abnormalit ies but showed a significant reduction in the number of bone marrow colony- forming unit erythroid (CFU-E)-derived colonies. This implies a defect of n ormal erythroid hematopoiesis affecting relatively late erythroid progenito r cells. We also show that when newborn Evil transgenic mice of these two l ines were infected with Cas-Br-M MuLV, tumor incidence was greatly enhanced in comparison with nontransgenic littermates, indicating an increased susc eptibility for leukemia development. Interestingly, analysis of a third fou nder line revealed that all male progeny consistently displayed severely im paired erythropoiesis with major defects in the bone marrow, spleen and per ipheral blood. Taken together, our results present the first evidence of Ev il disturbing normal erythropoiesis in vivo and provides evidence for coope rative potential of Evil in tumor progression.