Gene expression profiling of Hfe-/- liver and duodenum in mouse strains with differing susceptibilities to iron loading: identification of transcriptional regulatory targets of Hfe and potential hemochromatosis modifiers

doi:10.1186/gb-2007-8-10-r221

Genome Biology
Volume 8
Issue 10

Viewing options:

Abstract
Full text
PDF (726KB)
Additional files

Associated material:

PubMed record

Related literature:

Articles citing this article
on Google Scholar
on ISI Web of Science
on PubMed Central
Other articles by authors
on Google Scholar

Coppin H
Darnaud V
Kautz L
Meynard D
Aubry M
Mosser J
Martinez M
Roth MP

on PubMed

Coppin H
Darnaud V
Kautz L
Meynard D
Aubry M
Mosser J
Martinez M
Roth MP
Related articles/pages
on Google

on Google Scholar

on PubMed

Tools:

Post to:

Research

Gene expression profiling of Hfe^-/-liver and duodenum in mouse strains with differing susceptibilities to iron loading: identification of transcriptional regulatory targets of Hfe and potential hemochromatosis modifiers

Hélène Coppin¹^,2 , Valérie Darnaud¹^,2 , Léon Kautz¹^,2 , Delphine Meynard¹^,2 , Marc Aubry³^,4 , Jean Mosser³^,4 , Maria Martinez¹^,2 and Marie-Paule Roth¹^,2

¹INSERM, U563, Centre de Physiopathologie de Toulouse Purpan, Toulouse, F-31300 France

²Université Toulouse III Paul-Sabatier, IFR 30, Toulouse, F-31400 France

³CNRS, UMR6061, Génétique et Développement, Rennes, F-35000 France

⁴Université de Rennes 1, IFR 140, Rennes, F-35000 France

author email corresponding author email

Genome Biology 2007, 8:R221doi:10.1186/gb-2007-8-10-r221


Published:	18 October 2007

Abstract

Background

Hfe disruption in mouse leads to experimental hemochromatosis by a mechanism that remains elusive. Affymetrix GeneChip^®Mouse Genome 430 2.0 microarrays and bioinformatics tools were used to characterize patterns of gene expression in the liver and the duodenum of wild-type and Hfe-deficient B6 and D2 mice (two inbred mouse strains with divergent iron loading severity in response to Hfe disruption), to clarify the mechanisms of Hfe action, and to identify potential modifier genes.

Results

We identified 1,343 transcripts that were upregulated or downregulated in liver and 370 in duodenum of Hfe^-/-mice, as compared to wild-type mice of the same genetic background. In liver, Hfe disruption upregulated genes involved in antioxidant defense, reflecting mechanisms of hepatoprotection activated by iron overload. Hfe disruption also downregulated the expression of genes involved in fatty acid β-oxidation and cholesterol catabolism, and of genes participating in mitochondrial iron traffic, suggesting a link between Hfe and the mitochondrion in regulation of iron homeostasis. These latter alterations may contribute to the inappropriate iron deficiency signal sensed by the duodenal enterocytes of these mice, and the subsequent upregulation of the genes encoding the ferrireductase Dcytb and several iron transporters or facilitators of iron transport in the duodenum. In addition, for several genes differentially expressed between B6 and D2 mice, expression was regulated by loci overlapping with previously mapped Hfe-modifier loci.

Conclusion

The expression patterns identified in this study contribute novel insights into the mechanisms of Hfe action and potential candidate genes for iron loading severity.