Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-1-11
pubmed:abstractText
Hereditary hemochromatosis type 3 is an iron (Fe)-overload disorder caused by mutations in transferrin receptor 2 (TfR2). TfR2 is expressed highly in the liver and regulates Fe metabolism. The aim of this study was to investigate duodenal Fe absorption and hepatic Fe uptake in a TfR2 (Y245X) mutant mouse model of hereditary hemochromatosis type 3. Duodenal Fe absorption and hepatic Fe uptake were measured in vivo by 59Fe-labeled ascorbate in TfR2 mutant mice, wild-type mice, and Fe-loaded wild-type mice (2% dietary carbonyl Fe). Gene expression was measured by real-time RT-PCR. Liver nonheme Fe concentration increased progressively with age in TfR2 mutant mice compared with wild-type mice. Fe absorption (both duodenal Fe uptake and transfer) was increased in TfR2 mutant mice compared with wild-type mice. Likewise, expression of genes participating in duodenal Fe uptake (Dcytb, DMT1) and transfer (ferroportin) were increased in TfR2 mutant mice. Nearly all of the absorbed Fe was taken up rapidly by the liver. Despite hepatic Fe loading, hepcidin expression was decreased in TfR2 mutant mice compared with wild-type mice. Even when compared with Fe-loaded wild-type mice, TfR2 mutant mice had increased Fe absorption, increased duodenal Fe transport gene expression, increased liver Fe uptake, and decreased liver hepcidin expression. In conclusion, despite systemic Fe loading, Fe absorption and liver Fe uptake were increased in TfR2 mutant mice in association with decreased expression of hepcidin. These findings support a model in which TfR2 is a sensor of Fe status and regulates duodenal Fe absorption and liver Fe uptake.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0193-1857
pubmed:author
pubmed:issnType
Print
pubmed:volume
292
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
G323-8
pubmed:dateRevised
2007-12-3
pubmed:meshHeading
pubmed-meshheading:16935854-Animals, pubmed-meshheading:16935854-Base Sequence, pubmed-meshheading:16935854-Biological Transport, pubmed-meshheading:16935854-Crosses, Genetic, pubmed-meshheading:16935854-DNA Primers, pubmed-meshheading:16935854-Disease Models, Animal, pubmed-meshheading:16935854-Duodenum, pubmed-meshheading:16935854-Female, pubmed-meshheading:16935854-Ferritins, pubmed-meshheading:16935854-Hemochromatosis, pubmed-meshheading:16935854-Heterozygote Detection, pubmed-meshheading:16935854-Intestinal Absorption, pubmed-meshheading:16935854-Iron, pubmed-meshheading:16935854-Liver, pubmed-meshheading:16935854-Male, pubmed-meshheading:16935854-Mice, pubmed-meshheading:16935854-Mice, Inbred C57BL, pubmed-meshheading:16935854-Mice, Mutant Strains, pubmed-meshheading:16935854-Receptors, Transferrin
pubmed:year
2007
pubmed:articleTitle
Iron absorption and hepatic iron uptake are increased in a transferrin receptor 2 (Y245X) mutant mouse model of hemochromatosis type 3.
pubmed:affiliation
School of Medicine and Pharmacology, Fremantle Hospital, University of Western Australia, PO Box 480, Fremantle, 6959, WA, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural