Foetal erythropoiesis in steel mutant mice. II. Haemopoietic stem cells in foetal livers during development.

A rapid and reliable method of definitively identifying mutant (Sl/Sld) and wild type (+/+) mouse embryos in segregating litters is described, based on the mean cell volume determination of circulating foetal erythrocytes by an electronic particle counter. The mean cell volumes of yolk sac derived nucleated erythrocytes from +/+ and Sl/Sld embryos are similar, whereas the foetal liver derived non-nucleated red blood cells are much larger in Sl/Sld than +/+ embryos. There is no significant retardation in the growth of mutant embryos in spite of the severe anaemia which is macrocytic and normochromic. Evidence is also presented that the proportion of haemopoietic stem cells among hepatic erythroblasts, assayed by the macroscopic spleen colony technique, is higher in the mutant embryos, even though the total number of these progenitor cells present in each mutant foetal liver is less than the normal. Furthermore, these stem cells undergo active proliferation in Sl/Sld foetuses during development. The data indicate that the mutant Sl genes do not affect the primitive erythroid cell lineage derived from the yolk sac blood islands, but seriously interfere with the differentiation of the definitive erythroid cell lineage of foetal liver origin. It is further suggested that the mutant foetal liver fails to support or interferes with the normal rate of differentiation from immature precursor cells in to haemoglobinized erythroblasts. The reduction of total haemopoietic stem cells in mutant embryos may be secondary to this defect in cellular differentiation.