Quantitative evaluation of expression of iron-metabolism genes in ceruloplasmin-deficient mice.

Abstract

Aceruloplasminemia is an autosomal recessive disorder caused by mutations in the ceruloplasmin (CP) gene, and is characterized by a unique combination of neurovisceral iron overload and iron deficiency anemia. We generated CP-deficient (CP(-/-)) mice to investigate the functional involvement of CP in iron metabolism. The mice showed a marked iron overload in the liver and mild iron deficiency anemia. We examined the expression of iron-metabolism genes in the duodenum and liver using TaqMan RT-PCR. The divalent metal transporter 1 (DMT1), ferroportin 1 (FPN1), and hephaestin (HEPH) genes were not up-regulated in the duodenum from CP(-/-) mice. These data suggest that the mechanism of hepatic iron overload in aceruloplasminemia is quite different from that in hemochromatoses and atransferrinemia. In the liver, CP(-/-) mice showed no increase of gene expression for DMT1 and transferrin receptors (TFR and TFR2), indicating that none of the known pathways of iron uptake is activated in hepatocytes of CP(-/-) mice. This result supports the hypothesis that CP mainly acts to release iron from cells in the liver.

• Authors: Kanji Yamamoto, Kunihiro Yoshida, Yuko Miyagoe, Aki Ishikawa, Kazunori Hanaoka, Shozo Nomoto, Kazuma Kaneko, Shu-ichi Ikeda, Shin'ichi Takeda
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1588 Issue 3 Pg. 195-202 (Dec 12 2002) ISSN: 0006-3002 [Print] Netherlands
• PMID: 12393173 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cation Transport Proteins
• HEPH protein, human
• Heph protein, mouse
• Iron-Binding Proteins
• Membrane Proteins
• metal transporting protein 1
• solute carrier family 11- (proton-coupled divalent metal ion transporters), member 2
• Iron
• Ceruloplasmin

Topics

• Anemia, Iron-Deficiency (genetics, metabolism)
• Animals
• Cation Transport Proteins (genetics)
• Ceruloplasmin (deficiency, genetics)
• Disease Models, Animal
• Duodenum (metabolism)
• Gene Expression
• Hepatocytes (metabolism)
• Iron (analysis, blood, metabolism)
• Iron Overload (genetics)
• Iron-Binding Proteins (genetics)
• Kupffer Cells (metabolism)
• Liver (metabolism)
• Membrane Proteins (genetics)
• Mice
• Reverse Transcriptase Polymerase Chain Reaction