Mouse microcytic anaemia caused by a defect in the gene encoding the globin enhancer-binding protein NF-E2.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Peters, LL; Andrews, NC; Eicher, EM; Davidson, MB; Orkin, SH; Lux, SE

Published Date

  • April 22, 1993

Published In

Volume / Issue

  • 362 / 6422

Start / End Page

  • 768 - 770

PubMed ID

  • 8469289

International Standard Serial Number (ISSN)

  • 0028-0836

Digital Object Identifier (DOI)

  • 10.1038/362768a0


  • eng

Conference Location

  • England