MICROCYTIC ANEMIA IN MK MK MICE IS NOT CORRECTED BY RETROVIRAL-MEDIATED GENE-TRANSFER OF WILD-TYPE P45 NF-E2/

Mice homozygous for the mk mutation have a severe hypochromic, microcy tic anemia that is characterized by a decreased mean-corpuscular hemog lobin concentration and balanced alpha- and beta-globin-chain synthesi s. Transplantation studies have shown that the defect in homozygous mk /mk mice is intrinsic to both the hematopoietic system and the gut. Th e gene for the hematopoietic-specific transcription factor, p45 NF-E2, has been found to cosegregate with the mk phenotype and contain a poi nt mutation in mk/mk mice that results in an amino acid substitution ( V-173-->A). In order to test the hypothesis that this amino acid subst itution is responsible for the mk phenotype, we have used recombinant retroviruses to introduce wild-type p45 NF-E2 into the bone marrow of mk/mk mice. Despite gene transfer and expression of p45 NF-E2 in eryth roid cells, we found no evidence for correction of the phenotype in mk /mk mice. These results indicate that the ink mutation cannot be corre cted by enforced expression of wild-type p45 NF-E2 and suggest that th e V-173-->A mutation of the p45 NF-E2 gene is not the cause of anemia in mk/mk mice.