In Vivo Colony Forming Unit Population Sizes in Hypertransfused SI/SI^d Mice

Abstract

As a result of a genetic defect expressed in the stroma of the tissues supporting hematopoiesis rather than in the hematopoietic cells themselves, mice of genotype Sl/Sl ^d (Steel, Steel-Dickie mutant mice) suffer a chronic macrocytic anemia, and are extremely sensitive to ionizing radiation (11). Previously, it was hypothesized that the genetic defect disturbs erythropoiesis very early in the erythron, perhaps at the point of commitment of in vivo colony-forming units (CFU) to the erythrocytic cellular line of differentiation (8, 19). In an earlier study (9), this hypothesis was tested by measuring and comparing, in Sl/Sl ^d mice and their congenic +1+ littermates, population sizes of high self-renewal potential and low self-renewal potential CFU. It was reasoned that a block in stem cell differentiation occurring early in the erythron would result in a deficiency of the latter but not of the former. However, our study did not bear this hypothesis out. Rather, it led to the unexpected observation that all the stem cell populations in Sl/Si ^d mice, with the exception of the splenic CFU population, were reduced in size.