Duodenal mRNA expression of iron related genes in response to iron loading and iron deficiency in four strains of mice.
BACKGROUND
Although much progress has been made recently in characterising the proteins involved in duodenal iron trafficking, regulation of intestinal iron transport remains poorly understood. It is not known whether the level of mRNA expression of these recently described molecules is genetically regulated. This is of particular interest however as genetic factors are likely to determine differences in iron status among mouse strains and probably also contribute to the phenotypic variability seen with disruption of the haemochromatosis gene.


OBJECTIVE
To investigate this issue, we examined concomitant variations in duodenal cytochrome b (Dcytb), divalent metal transporter 1 (DMT1), ferroportin 1 (FPN1), hephaestin, stimulator of Fe transport (SFT), HFE, and transferrin receptor 1 (TfR1) transcripts in response to different dietary iron contents in the four mouse strains C57BL/6, DBA/2, CBA, and 129/Sv.


METHODS
Six mice of each strain were fed normal levels of dietary iron, six were subjected to the same diet supplemented with 2% carbonyl iron, and six were fed an iron deficient diet.


METHODS
Quantification of mRNAs isolated from the duodenum was performed using real time reverse transcription-polymerase chain reaction.


RESULTS
There was a significant increase in mRNA expression of Dcytb, DMT1, FPN1, and TfR1 when mice were fed an iron deficient diet, and a significant decrease in mRNA expression of these molecules when mice were fed an iron supplemented diet. Strain to strain differences were observed not only in serum transferrin saturations, with C57BL/6 mice having the lowest values, but also in hepatic iron stores and in duodenal mRNA expression of Dcytb, DMT1, FPN1, hephaestin, HFE, and TfR1.


CONCLUSIONS
The results favour some degree of genetic control of mRNA levels of these molecules.
Dupic
F
F
Unité de Physiopathologie Cellulaire et Moléculaire, CNRS UPR 2163, CHU Purpan, Toulouse, France.
Fruchon
S
S
Bensaid
M
M
Loreal
O
O
Brissot
P
P
Borot
N
N
Roth
M P
MP
Coppin
H
H
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D027682:Cation Transport Proteins / Q000235:genetics; D003573:Cytochrome b Group / Q000235:genetics; D004386:Duodenum / Q000378:metabolism*; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D007413:Intestinal Mucosa / Q000378:metabolism*; D000090463:Iron Deficiencies; D019266:Iron, Dietary / Q000008:administration & dosage*; D033862:Iron-Binding Proteins / Q000235:genetics; D008099:Liver / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains; D012333:RNA, Messenger / Q000032:analysis*; D011990:Receptors, Transferrin / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013045:Species Specificity; D014168:Transferrin / Q000032:analysis; D044763:Ubiquitin-Conjugating Enzymes; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2
D002352:Carrier Proteins; D027682:Cation Transport Proteins; D003573:Cytochrome b Group; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D019266:Iron, Dietary; D033862:Iron-Binding Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D011990:Receptors, Transferrin; D014168:Transferrin; D044763:Ubiquitin-Conjugating Enzymes; D000098742:Ferroportin; D000099236:Solute Carrier Family 11, Member 2; C492164:HEPH protein, human; C117324:Heph protein, mouse; C499535:Hfe protein, mouse; C490789:Ube2d1 protein, mouse