title: Microcytic anemia in mk/mk mice is not corrected by retroviral-mediated gene transfer of wild-type p45 NF-E2.
abstract: Mice homozygous for the mk mutation have a severe hypochromic, microcytic anemia that is characterized by a decreased mean-corpuscular hemoglobin concentration and balanced alpha- and beta-globin-chain synthesis. Transplantation studies have shown that the defect in homozygous mk/mk mice is intrinsic to both the hematopoietic system and the gut. The gene for the hematopoietic-specific transcription factor, p45 NF-E2, has been found to cosegregate with the mk phenotype and contain a point mutation in mk/mk mice that results in an amino acid substitution (173V-->A). In order to test the hypothesis that this amino acid substitution 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 erythroid cells, we found no evidence for correction of the phenotype in mk/mk mice. These results indicate that the mk mutation cannot be corrected by enforced expression of wild-type p45 NF-E2 and suggest that the 173V-->A mutation of the p45 NF-E2 gene is not the cause of anemia in mk/mk mice.
authors.affiliation: Department of Biochemistry, Saint Jude Children's Research Hospital, Memphis, TN.
authors.forename: P A
authors.initials: PA
authors.lastname: Ney
authors.forename: S F
authors.initials: SF
authors.lastname: Farina
authors.forename: D M
authors.initials: DM
authors.lastname: Bodine
authors.forename: N C
authors.initials: NC
authors.lastname: Andrews
authors.forename: S H
authors.initials: SH
authors.lastname: Orkin
authors.forename: A W
authors.initials: AW
authors.lastname: Neinhuis
mesh_terms: D000199:Actins / Q000235:genetics; D000740:Anemia / Q000628:therapy*; D000818:Animals; D001483:Base Sequence; D001853:Bone Marrow / Q000378:metabolism; D004274:DNA, Recombinant / Q000627:therapeutic use; D004268:DNA-Binding Proteins / Q000235:genetics*; D050981:Erythroid-Specific DNA-Binding Factors; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D005914:Globins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D050983:NF-E2 Transcription Factor; D050984:NF-E2 Transcription Factor, p45 Subunit; D017354:Point Mutation; D012190:Retroviridae / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D000199:Actins; D004274:DNA, Recombinant; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050983:NF-E2 Transcription Factor; D050984:NF-E2 Transcription Factor, p45 Subunit; C494693:Nfe2 protein, mouse; D014157:Transcription Factors; D005914:Globins