Abstract
Mice homozygous for Hertwig's anemia, an/an, have a mild macrocytic anemia and are refractory to the potentially curative action of exogenously administered erythropoietin (EP). Both red and white blood cell numbers are decreased. One possible explanation is that a precursor stem cell population is in short supply. We have examined this possibility through comparisons of CFU-S, BFU-E, and CFU-E numbers in an/an and +/+ mouse bone marrow. The response of erythroid-committed stem cells to EP in vitro has also been determined. Our findings suggest that EP resistance is due to diminished numbers rather than decreased EP sensitivity of responsive cells. In mice with Hertwig's anemia, the relative numbers of both BFU-E and CFU-E are reduced. The erythroid-committed stem cells are more severely affected than their progenitors, the CFU-S. The data show that cells are lost during the progressive differentiation from stem cell to erythrocyte.