title: Mouse microcytic anaemia caused by a defect in the gene encoding the globin enhancer-binding protein NF-E2.
abstract: The nuclear DNA-binding protein NF-E2 is thought to mediate the powerful erythroid enhancer activity of the alpha- and beta-globin locus control regions and participates in the control of genes encoding two enzymes of haem biosynthesis (porphobilinogen deaminase and ferrochelatase). The major component of NF-E2 is a 45K polypeptide (designated p45 NF-E2) that belongs to the basic region-leucine zipper family of transcription factors. This subunit of NF-E2 is specifically expressed in haematopoietic progenitor cells and differentiated cells of the erythroid, megakaryocyte and mast cell lineages. The gene encoding p45 NF-E2 (murine gene Nfe2) has been mapped to mouse chromosome 15 near the mutation microcytosis (mk). Homozygous mk mice have severe hypochromic microcytic anaemia as a result of decreased globin synthesis and defects in intestinal and erythroid iron absorption. Here we investigate whether the mk mutation lies within Nfe2 by characterizing the p45 NF-E2 gene and determining its DNA sequence in wild-type and mk alleles. The mk allele carries a missense mutation that causes substitution of valine by alanine at amino acid 173 of the p45 NF-E2 protein. Expression of p45 NF-E2 messenger RNA was detected in erythroid tissues of normal mice and in the duodenum of normal and severely anaemic beta-thalassaemic (Hbbd-th3/Hbbd-th3) mice. We propose that the mk mutation results in an impaired form of NF-E2 which fails to regulate both globin production and iron metabolism properly.
authors: Division of Hematology/Oncology, Children's Hospital, Boston, Massachusetts.
authors: L L
authors: LL
authors: Peters
authors: N C
authors: NC
authors: Andrews
authors: E M
authors: EM
authors: Eicher
authors: M B
authors: MB
authors: Davidson
authors: S H
authors: SH
authors: Orkin
authors: S E
authors: SE
authors: Lux
mesh_terms: D000595:Amino Acid Sequence; D000740:Anemia / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D004247:DNA; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004386:Duodenum / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D050981:Erythroid-Specific DNA-Binding Factors; D005914:Globins / Q000235:genetics*; D007501:Iron / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D009154:Mutation; D050983:NF-E2 Transcription Factor; D050984:NF-E2 Transcription Factor, p45 Subunit; D009928:Organ Specificity; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D017086:beta-Thalassemia / Q000378:metabolism
chemical_list: 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; D004247:DNA; D007501:Iron