Quantitative evaluation of expression of iron-metabolism genes in ceruloplasmin-deficient mice.
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.
Yamamoto
Kanji
K
The Third Department of Medicine, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
Yoshida
Kunihiro
K
Miyagoe
Yuko
Y
Ishikawa
Aki
A
Hanaoka
Kazunori
K
Nomoto
Shozo
S
Kaneko
Kazuma
K
Ikeda
Shu-ichi
S
Takeda
Shin'ichi
S
D018798:Anemia, Iron-Deficiency / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D027682:Cation Transport Proteins / Q000235:genetics; D002570:Ceruloplasmin / Q000172:deficiency* / Q000235:genetics; D004195:Disease Models, Animal; D004386:Duodenum / Q000378:metabolism; D015870:Gene Expression; D022781:Hepatocytes / Q000378:metabolism; D007501:Iron / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D019190:Iron Overload / Q000235:genetics*; D033862:Iron-Binding Proteins / Q000235:genetics; D007728:Kupffer Cells / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2
D027682:Cation Transport Proteins; D002570:Ceruloplasmin; D007501:Iron; D033862:Iron-Binding Proteins; D008565:Membrane Proteins; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2; C492164:HEPH protein, human; C117324:Heph protein, mouse