mRNA expression of iron regulatory genes in beta-thalassemia intermedia and beta-thalassemia major mouse models

Am J Hematol. 2006 Jul;81(7):479-83. doi: 10.1002/ajh.20549.

Abstract

beta-Thalassemia is an inherited anemia in which synthesis of the hemoglobin beta-chain is decreased. The excess unmatched alpha-globin chains accumulate in the growing erythroid precursors, causing their premature death (ineffective erythropoiesis). Clinical features of beta-thalassemia include variably severe anemia and iron accumulation due to increased intestinal iron absorption. The most anemic patients require regular blood transfusions, which exacerbate their iron overload and result in damage to vital organs. The hepatic peptide hepcidin, a key regulator of iron metabolism in mammals, was recently found to be low in the urine of beta-thalassemia patients, compared with healthy controls, despite their iron overload. In our work, we measured by RQ-PCR the liver mRNA expression of hepcidin and other iron regulatory genes in beta-thalassemia major mouse model (C57Bl/6 Hbb(th3/th3)), and compared it with beta-thalassemia intermedia mouse model (C57Bl/6 Hbb(th3/+)) and control mice. We found decreased expression of hepcidin and TfR2 and increased expression of TfR1 and NGAL in the beta-thalassemia mouse models, compared with the control mice. Significant down-regulation of hepcidin expression in beta-thalassemia major, despite iron overload, might explain the increased iron absorption typically observed in thalassemia.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins / biosynthesis
  • Acute-Phase Proteins / genetics
  • Animals
  • Antimicrobial Cationic Peptides / genetics*
  • Antimicrobial Cationic Peptides / urine
  • Disease Models, Animal
  • Down-Regulation / genetics
  • Erythroid Precursor Cells / metabolism
  • Erythroid Precursor Cells / pathology
  • Erythropoiesis / genetics
  • Female
  • Gene Expression Profiling
  • Genes, Regulator / genetics*
  • Globins / genetics
  • Globins / metabolism
  • Hepcidins
  • Humans
  • Intestinal Absorption / genetics*
  • Iron / metabolism*
  • Iron Overload / genetics
  • Iron Overload / metabolism
  • Lipocalin-2
  • Lipocalins
  • Mice
  • Oncogene Proteins / biosynthesis
  • Oncogene Proteins / genetics
  • Receptors, Transferrin / biosynthesis
  • Receptors, Transferrin / genetics
  • beta-Thalassemia / genetics*
  • beta-Thalassemia / metabolism
  • beta-Thalassemia / pathology

Substances

  • Acute-Phase Proteins
  • Antimicrobial Cationic Peptides
  • HAMP protein, human
  • Hamp protein, mouse
  • Hepcidins
  • Lipocalin-2
  • Lipocalins
  • Oncogene Proteins
  • Receptors, Transferrin
  • Tfrc protein, mouse
  • Lcn2 protein, mouse
  • Globins
  • Iron