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- Title
Iron handling and gene expression of the divalent metal transporter, DMT1, in the kidney of the anemic Belgrade ( b) rat.
- Authors
Ferguson, Carole J.; Wareing, Mark; Delannoy, Mathieu; Fenton, Robert; McLarnon, Stuart J.; Ashton, Nicholas; Cox, Alan G.; McMahon, Raymond F.T.; Garrick, Laura M.; Green, Roger; Smith, Craig P.; Riccardi, Daniela
- Abstract
Iron handling and gene expression of the divalent metal transporter, DMT1, in the kidney of the anemic Belgrade ( b ) rat. We have previously shown that the rat kidney reabsorbs metabolically significant amounts of iron and that it expresses the divalent metal transporter 1, DMT1. The Belgrade ( b) rat carries a mutation in DMT1 gene, which causes hypochromic, microcytic anemia due to impaired intestinal iron absorption and transport of iron out of the transferrin cycle endosome. In the duodenum of b/b rats, expression of DMT1 mRNA and protein is increased, suggesting a feedback regulation by iron stores. The aim of this study was to investigate iron handling and DMT1 expression in the kidneys of Belgrade rats. Animals were maintained for 3 weeks on a synthetic diet containing 185 mg/kg iron (FeSO4), after which functional and molecular parameters were analyzed in male heterozygous ( +/b) and homozygous ( b/b) rats ( N = 4 to 6 for each group). Serum iron concentration was significantly higher in b/b compared to +/ b rats while urinary iron excretion rates were unchanged in b/b compared to +/ b rats. Northern analysis using a rat DMT1 probe showed comparable mRNA levels between +/ b and b/b animals. Western analysis and immunofluorescence microscopy performed using a polyclonal antibody against rat DMT1 showed that DMT1-specific immunoreactivity was almost absent in the kidneys of b/b rats compared to that seen in +/ b animals. Our results indicate that the G185R mutation of DMT1 causes protein instability in the kidneys of b/b rats. Given that +/b and b/b rats excrete comparable amounts of iron, the lack of DMT1 protein is compensated by an alternative, yet to be identified, mechanism.
- Subjects
GENE expression; KIDNEYS
- Publication
Kidney International, 2003, Vol 64, Issue 5, p1755
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1046/j.1523-1755.2003.00274.x