The competitive ability of stem cells from mice with Hertwig's anemia

Mice homozygous for the gene, an, have a macrocytic, normochromic anemia. In this report, attempts have been made to cure Hertwig's anemia (an/an) by injecting genetically normal (+/+) stem cells. The anemia of unirradiated an/an mice was alleviated but not completely cured by injection of as many as 3 X 10(7) +/+ bone marrow cells. Lethal irradiation of the an/an recipients was necessary before injections of 10(7) +/+ marrow cells were effective in normalizing the blood parameters. The inability to achieve normal blood values without first destroying the host's own stem cells suggested that the indigenous an/an cells compete effectively with injected +/+ cells. This hypothesis was tested by injecting varying numbers of stem cells from C57BL/6J-+/+ mice, together with stem cells from either WBB6F1-an/an or, as controls, from their WBB6F1-+/+ littermates, into lethally irradiated hosts. The C57BL/6J and WBB6F1 mice have electrophoretically distinguishable hemoglobins. The an/an cells are able to compete in the repopulation of the host hematopoietic tissue as shown by the presence of WBB6F1 hemoglobin in the recipients. The cells from mice with Hertwig's anemia, however, do not compete as effectively as do the same number of cells from the +/+ littermates. These results indicate that the pluripotent hematopoietic stem cells of an/an mice are reduced in number, seeding capacity, or proliferative potential.