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四种品系小鼠十二指肠中铁相关基因在铁负荷和缺铁状态下的mRNA表达

Duodenal mRNA expression of iron related genes in response to iron loading and iron deficiency in four strains of mice.

作者信息

Dupic F, Fruchon S, Bensaid M, Loreal O, Brissot P, Borot N, Roth M P, Coppin H

机构信息

Unité de Physiopathologie Cellulaire et Moléculaire, CNRS UPR 2163, CHU Purpan, Toulouse, France.

出版信息

Gut. 2002 Nov;51(5):648-53. doi: 10.1136/gut.51.5.648.

Abstract

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 (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.

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.

摘要

背景

尽管最近在十二指肠铁转运相关蛋白的特性研究方面取得了很大进展,但肠道铁转运的调控仍知之甚少。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。然而,这一点特别值得关注,因为遗传因素可能决定小鼠品系间铁状态的差异,并且可能也导致了血色素沉着症基因破坏时出现的表型变异性。

目的

为了研究这个问题,我们检测了C57BL/6、DBA/2、CBA和129/Sv这四种小鼠品系在不同饮食铁含量条件下,十二指肠细胞色素b(Dcytb)、二价金属转运体1(DMT1)、铁转运蛋白1(FPN1)、高铁氧化酶、铁转运刺激因子(SFT)、血色素沉着症蛋白(HFE)和转铁蛋白受体1(TfR1)转录本的伴随变化。

对象

每个品系的六只小鼠喂食正常水平的饮食铁,六只喂食添加2%羰基铁的相同饮食,六只喂食缺铁饮食。

方法

使用实时逆转录聚合酶链反应对从十二指肠分离的mRNA进行定量。

结果

当小鼠喂食缺铁饮食时,Dcytb、DMT1、FPN1和TfR1的mRNA表达显著增加;当小鼠喂食补铁饮食时,这些分子的mRNA表达显著降低。不仅在血清转铁蛋白饱和度方面观察到品系间差异(C57BL/6小鼠的值最低),而且在肝脏铁储存以及Dcytb、DMT1、FPN1、高铁氧化酶、HFE和TfR1的十二指肠mRNA表达方面也观察到品系间差异。

结论

结果支持这些分子的mRNA水平存在一定程度的基因控制。

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