Fv-2 locus controls the proportion of erythropoietic progenitor cells (BFU-E) synthesizing DNA in normal mice

We have found that Fv-2 on chromosome 9 of the mouse, the locus originally identified as a major determinant of host susceptibility (Fv-2s) or resistance (Fv-2r) to Friend leukemia virus in mice, also functions in uninfected animals, where it determines whether a high (Fv-2s) or low (Fv-2r) proportion of erythropoietic progenitor cells BFU-E are normally engaged in DNA synthesis. Adult mice belonging to five inbred strains of genotype Fv-2rr, two inbred strains and three congenic strains of genotype Fv-2ss, two kinds of F1 hybrid of genotype Fv-2rs, and appropriate controls were given high specific activity 3H--thymidine intravenously for 1 hr and their bone marrow and spleen cells were assayed for surviving BFU-E at 7 days and CFU-E at 2 days in plasma culture. A high proportion of BFU-E in all Fv-2ss and Fv-2rs mice were killed, but all or nearly all of the BFU-E in Fv-2rr mice survived exposure to 3H--thymidine. The allelic difference of Fv-2 had no significant effect on the proportion of other progenitor or stem cells (CFU-E, CFU-C or CFU-S) normally undergoing DNA synthesis in the hemopoietic tissues, or on the hemoglobin concentration, red blood cells, hematocrit, total of differential white blood cell counts in the peripheral blood of these animals. While a few or no BFU-E were killed by 3H--thymidine in adult B6 (Fv-2rr) mice, a high proportion of BFU-E were killed by 3H--thymidine in these animals when they were less than 7 weeks old. Bleeding of adult B6 mice or lethal irradiation followed by repopulation by syngeneic bone marrow cells rendered a high proportion of their BFU-E vulnerable to 3H--thymidine. BFU-E of adult B6 mice which in vivo were unaffected by 3H--thymidine were rapidly killed when exposed to 3H--thymidine in vitro. Fv-2 thus seems to act at or near the G1-S or G0-S boundary to influence the rate or probability of transition between the nonDNA-synthesizing and the DNA-synthesizing states of BFU-E. The gene that controls susceptibility or resistance to a murine erythroleukemia virus appears also to be a regulatory gene that controls the proliferative behaviour of normal cells at a specific stage of erythropoietic differentiation.