The significance of the mutated divalent metal transporter (DMT1) on iron transport into the Belgrade rat brain.
Brain iron transport and distributional pattern of divalent metal transporter I (DMT1) were studied in homozygous Belgrade rats (b/b) which suffer from a mutation in the DMT1 gene. In adult rats, brain uptake of transferrin-bound iron injected intravenously (i.v.) was significantly lower compared with that in heterozygous Belgrade (+/b) and Wistar rats, whereas transferrin uptake was identical. The difference in iron uptake was not apparent until 30 min after injection. The brain iron concentration was lower, and neuronal transferrin receptor-immunoreactivity higher, in adult b/b rats, thus confirming their iron-deficient stage. Antibodies targeting different sites on the DMT1 molecule consistently detected DMT1 in neurones and choroid plexus at the same level irrespective of strain, but failed to detect DMT1 in brain capillary endothelial cells (BCECs), or macro- or microglial cells. The absence of DMT1 in BCECs was confirmed in immunoblots of purified BCECs. DMT1 was virtually undetectable in neurones of rats aged 18 post-natal days irrespective of strain. Neuronal expression of transferrin receptors and DMT1 in adult rats implies that neurones at this age acquire iron by receptor-mediated endocytosis of transferrin followed by iron transport out of endosomes mediated by DMT1. The existence of the mutated DMT1 molecule in neurones suggests that the low cerebral iron uptake in b/b rats derives from a reduced neuronal uptake rather than an impaired iron transport through the blood-brain barrier.
Moos
Torben
T
Department of Medical Anatomy, University of Copenhagen, Copenhagen, Denmark. T.Moos@mai.ku.dk
Morgan
Evan H
EH
D000818:Animals; D001921:Brain / Q000098:blood supply / Q000166:cytology / Q000378:metabolism*; D002196:Capillaries / Q000166:cytology; D027682:Cation Transport Proteins / Q000235:genetics* / Q000378:metabolism*; D004386:Duodenum / Q000166:cytology / Q000378:metabolism; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D015151:Immunoblotting; D017136:Ion Transport / Q000235:genetics; D007501:Iron / Q000378:metabolism* / Q000493:pharmacokinetics; D033862:Iron-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000378:metabolism; D009154:Mutation; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009928:Organ Specificity; D051381:Rats; D011922:Rats, Mutant Strains; D017208:Rats, Wistar; D013045:Species Specificity; D014168:Transferrin / Q000493:pharmacokinetics; D000099236:Solute Carrier Family 11, Member 2
D027682:Cation Transport Proteins; D007501:Iron; D033862:Iron-Binding Proteins; D014168:Transferrin; D000099236:Solute Carrier Family 11, Member 2