Duodenal mRNA expression of iron related genes in response to iron loading and iron deficiency in four strains of mice
Duodenal mRNA expression of iron related genes in response to iron loading and iron deficiency in four strains of mice
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DOI：
10.1136/gut.51.5.648
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发表时间：
2002-11-01
期刊：
影响因子：
24.5
通讯作者：
Coppin, H
中科院分区：
文献类型：
--
作者：
Dupic, F;Fruchon, S;Coppin, H
背景：虽然最近在描述参与十二指肠铁运输的蛋白质方面取得了很大进展，但对肠道铁运输的调控仍然知之甚少。目前尚不清楚这些最近描述的分子的mRNA表达水平是否受基因调控。这是特别有趣的，因为遗传因素可能决定了小鼠品系之间铁状态的差异，也可能导致血色素沉着病基因破坏的表型变异。目的：为了探讨这一问题，我们研究了四种小鼠品系C57BL/6、DBA/2、CBA和129/Sv中十二指肠细胞色素b （Dcytb）、二价金属转运蛋白1 （DMT1）、铁转运蛋白1 （FPN1）、肝蛋白酶、铁转运刺激因子（SIFT）、HFE和转铁蛋白受体1 （TfR 1）转录物在不同膳食铁含量下的变化。实验对象：每品系6只小鼠饲喂正常铁水平的饲料，6只饲喂添加2%羰基铁的饲料，6只饲喂缺铁饲料。方法：采用实时逆转录-聚合酶链反应对十二指肠分离的mrna进行定量分析。结果：缺铁小鼠Dcytb、DMT1、FPN1和TfR1 mRNA表达量显著升高，补铁小鼠Dcytb、DMT1、FPN1和TfR1 mRNA表达量显著降低。菌株间不仅血清转铁蛋白饱和度存在差异（以C57BL/6小鼠最低），而且肝脏铁储量和十二指肠Dcytb、DMT1、FPN1、hephaestin、HFE和TfR1 mRNA表达也存在差异。结论：这些结果在一定程度上支持这些分子mRNA水平的遗传控制。
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.Aims: 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 (SIFT), HFE, and transferrin receptor 1 (TfR 1) transcripts in response to different dietary iron contents in the four mouse strains C57BL/6, DBA/2, CBA and 129/Sv.Subjects: 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.