Temporal Replacement of Donor Erythrocytes and Leukocytes in Nonanemic W44-'/W44J and Severely Anemic W/W' Mice

mice in- EVERE MACROCYTIC anemia, deficiency of mega- S karyocytes, and reduction of mast cell numbers are characteristics of W/W" mice.' The hematopoietic defects are ascribed to a deficiency of precursor stem cells. In support of this hypothesis are the following: Firstly, all mice tested with mutations at the W locus, either as homozygotes or as double heterozygotes, accept congenic normal mar- row grafts without prior irradiati~n.'.~ Secondly, the W/W mice are much more sensitive to total body irradiation than are their normal littermates.* Finally, the W/W mice are deficient in the hematopoietic lineages descended from the totipotent hematopoietic stem cells (TSC).4-8 One would predict that, if the mutant mice do lack TSCs, all host peripheral blood cells would be completely and rapidly replaced after injection of donor +/+ cells and that the rate of repopulation would be determined primarily by the life span of the host cells. Previously, we injected 1 x l@ marrow cells that con- tained just sufficient TSC9 to replace the hematopoietic cells in WIW" mice and monitored repopulation." Com- plete host erythrocyte replacement preceeded that of leuko- cytes, platelets, and lymphocytes. Our results suggest that in W/W mice more severe defects occur in the erythroid lineage than in other lineages derived from the TSCs. The data were unexpected because we predicted, based on the