Genetic Control of Hematopoietic Kinetics Revealed by Analyses of Allophenic Mice and Stem Cell Suicide

The pluripotential hematopoietic stem cell is influenced by at least one gene that differs between DBA/2 and C3H/He, and C57BL/6 inbred mouse strains. This gene(s) manifests itself by its effect on susceptibility to killing of spleen colony forming cells (CFU-S) caused by hydroxyurea (HU). In strains DBA/2 and C3H/He 20% of the CFU-S population is normally in S phase whereas practically none from strain C57BL/6 are synthesizing DNA. On the other hand, in C57BL/6 in equilibrium DBA/2 allophenic mice we observed that the proportion of DBA/2 erythrocytes was higher than the proportion of DBA/2 lymphocytes; the fraction of platelets and neutrophils with the DBA/2 genotype fell between the values for erythrocytes and lymphocytes. Control experiments using mice congenic at the Fv-2 locus confirm that in both situations we are examining effects of a gene(s) other than Fv-2. For the effect on the S phase fraction of CFU-S, we refer to the gene(s) as Stk (stem cell kinetics). We suggest that the observed skewing in composition among the various mature blood cell types in C57BL/6 in equilibrium DBA/2 allophenic mice is caused by allelic variants of the Stk gene. Such variation would favor the formation of DBA/2 erythrocytes, platelets, and neutrophils over those of the C57BL/6 genotype.