Expression of stimulator of Fe transport is not enhanced in Hfe knockout mice.
Hfe knockout (-/-) mice recapitulate many of the biochemical abnormalities of hereditary hemochromatosis (HH), but the molecular mechanisms involved in the etiology of iron overload in HH remain poorly understood. It was found previously that livers of patients with HH contained 5-fold higher SFT (stimulator of Fe transport) mRNA levels relative to subjects without HH. Because this observation suggests a possible role for SFT in HH, we investigated SFT mRNA expression in Hfe(-/-) mice. The 4- and 10-wk-old Hfe(-/-) mice do not have elevated levels of hepatic SFT transcripts relative to age-matched Hfe(+/+) mice, despite having 2.2- and 3.3-fold greater hepatic nonheme iron concentrations, respectively. Northern blot analyses of various mouse tissues revealed that SFT is widely expressed. The novel observation that SFT transcripts are abundant in brain prompted a comparison of SFT transcript levels and nonheme iron levels in the brains of Hfe(+/+) and Hfe(-/-) mice. Neither SFT mRNA levels nor nonheme iron levels differed between groups. Further comparisons of Hfe(-/-) and Hfe(+/+) mouse tissues revealed no significant differences in SFT mRNA levels in duodenum, the site of increased iron absorption in HH. Important distinctions between Hfe(-/-) mice and HH patients include not only differences in the relative rate and magnitude of iron loading but also the lack of fibrosis and phlebotomy treatment in the knockout animals.
Knutson
M D
MD
Department of Nutrition, Harvard School of Public Health, Brigham & Women's Hospital, Boston, Massachusetts 02115, USA.
Levy
J E
JE
Andrews
N C
NC
Wessling-Resnick
M
M
D000818:Animals; D015152:Blotting, Northern; D001921:Brain / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D018076:DNA, Complementary; D004386:Duodenum / Q000378:metabolism; D005260:Female; D006680:HLA Antigens / Q000235:genetics* / Q000378:metabolism; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000378:metabolism; D007501:Iron / Q000493:pharmacokinetics*; D033862:Iron-Binding Proteins; D008099:Liver / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D044763:Ubiquitin-Conjugating Enzymes
D002352:Carrier Proteins; D018076:DNA, Complementary; D006680:HLA Antigens; D000071020:Hemochromatosis Protein; C499535:Hfe protein, mouse; D015395:Histocompatibility Antigens Class I; D033862:Iron-Binding Proteins; D008565:Membrane Proteins; D007501:Iron; C490789:Ube2d1 protein, mouse; D044763:Ubiquitin-Conjugating Enzymes