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

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...
Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Coppin, Hélène [verfasserIn] Darnaud, Valérie Kautz, Léon Meynard, Delphine Aubry, Marc Mosser, Jean Martinez, Maria Roth, Marie-Paule

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2007

Schlagwörter:	Iron Overload Additional Data File Iron Metabolism Hemochromatosis Hereditary Hemochromatosis

Anmerkung:	© Coppin et al.; licensee BioMed Central Ltd. 2007. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (

Übergeordnetes Werk:	Enthalten in: Genome biology - London : BioMed Central, 2000, 8(2007), 10 vom: 18. Okt.
Übergeordnetes Werk:	volume:8 ; year:2007 ; number:10 ; day:18 ; month:10

Links:	Volltext

DOI / URN:	10.1186/gb-2007-8-10-r221

Katalog-ID:	SPR029997569

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520			\|a 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.
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allfields	10.1186/gb-2007-8-10-r221 doi (DE-627)SPR029997569 (SPR)gb-2007-8-10-r221-e DE-627 ger DE-627 rakwb eng Coppin, Hélène verfasserin aut 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 2007 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Coppin et al.; licensee BioMed Central Ltd. 2007. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License ( 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. Iron Overload (dpeaa)DE-He213 Additional Data File (dpeaa)DE-He213 Iron Metabolism (dpeaa)DE-He213 Hemochromatosis (dpeaa)DE-He213 Hereditary Hemochromatosis (dpeaa)DE-He213 Darnaud, Valérie aut Kautz, Léon aut Meynard, Delphine aut Aubry, Marc aut Mosser, Jean aut Martinez, Maria aut Roth, Marie-Paule aut Enthalten in Genome biology London : BioMed Central, 2000 8(2007), 10 vom: 18. Okt. (DE-627)326173617 (DE-600)2040529-7 1474-760X nnns volume:8 year:2007 number:10 day:18 month:10 https://dx.doi.org/10.1186/gb-2007-8-10-r221 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2007 10 18 10
spelling	10.1186/gb-2007-8-10-r221 doi (DE-627)SPR029997569 (SPR)gb-2007-8-10-r221-e DE-627 ger DE-627 rakwb eng Coppin, Hélène verfasserin aut 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 2007 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Coppin et al.; licensee BioMed Central Ltd. 2007. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License ( 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. Iron Overload (dpeaa)DE-He213 Additional Data File (dpeaa)DE-He213 Iron Metabolism (dpeaa)DE-He213 Hemochromatosis (dpeaa)DE-He213 Hereditary Hemochromatosis (dpeaa)DE-He213 Darnaud, Valérie aut Kautz, Léon aut Meynard, Delphine aut Aubry, Marc aut Mosser, Jean aut Martinez, Maria aut Roth, Marie-Paule aut Enthalten in Genome biology London : BioMed Central, 2000 8(2007), 10 vom: 18. Okt. (DE-627)326173617 (DE-600)2040529-7 1474-760X nnns volume:8 year:2007 number:10 day:18 month:10 https://dx.doi.org/10.1186/gb-2007-8-10-r221 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2007 10 18 10
allfields_unstemmed	10.1186/gb-2007-8-10-r221 doi (DE-627)SPR029997569 (SPR)gb-2007-8-10-r221-e DE-627 ger DE-627 rakwb eng Coppin, Hélène verfasserin aut 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 2007 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Coppin et al.; licensee BioMed Central Ltd. 2007. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License ( 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. Iron Overload (dpeaa)DE-He213 Additional Data File (dpeaa)DE-He213 Iron Metabolism (dpeaa)DE-He213 Hemochromatosis (dpeaa)DE-He213 Hereditary Hemochromatosis (dpeaa)DE-He213 Darnaud, Valérie aut Kautz, Léon aut Meynard, Delphine aut Aubry, Marc aut Mosser, Jean aut Martinez, Maria aut Roth, Marie-Paule aut Enthalten in Genome biology London : BioMed Central, 2000 8(2007), 10 vom: 18. Okt. (DE-627)326173617 (DE-600)2040529-7 1474-760X nnns volume:8 year:2007 number:10 day:18 month:10 https://dx.doi.org/10.1186/gb-2007-8-10-r221 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2007 10 18 10
allfieldsGer	10.1186/gb-2007-8-10-r221 doi (DE-627)SPR029997569 (SPR)gb-2007-8-10-r221-e DE-627 ger DE-627 rakwb eng Coppin, Hélène verfasserin aut 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 2007 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Coppin et al.; licensee BioMed Central Ltd. 2007. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License ( 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. Iron Overload (dpeaa)DE-He213 Additional Data File (dpeaa)DE-He213 Iron Metabolism (dpeaa)DE-He213 Hemochromatosis (dpeaa)DE-He213 Hereditary Hemochromatosis (dpeaa)DE-He213 Darnaud, Valérie aut Kautz, Léon aut Meynard, Delphine aut Aubry, Marc aut Mosser, Jean aut Martinez, Maria aut Roth, Marie-Paule aut Enthalten in Genome biology London : BioMed Central, 2000 8(2007), 10 vom: 18. Okt. (DE-627)326173617 (DE-600)2040529-7 1474-760X nnns volume:8 year:2007 number:10 day:18 month:10 https://dx.doi.org/10.1186/gb-2007-8-10-r221 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2007 10 18 10
allfieldsSound	10.1186/gb-2007-8-10-r221 doi (DE-627)SPR029997569 (SPR)gb-2007-8-10-r221-e DE-627 ger DE-627 rakwb eng Coppin, Hélène verfasserin aut 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 2007 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Coppin et al.; licensee BioMed Central Ltd. 2007. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License ( 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. Iron Overload (dpeaa)DE-He213 Additional Data File (dpeaa)DE-He213 Iron Metabolism (dpeaa)DE-He213 Hemochromatosis (dpeaa)DE-He213 Hereditary Hemochromatosis (dpeaa)DE-He213 Darnaud, Valérie aut Kautz, Léon aut Meynard, Delphine aut Aubry, Marc aut Mosser, Jean aut Martinez, Maria aut Roth, Marie-Paule aut Enthalten in Genome biology London : BioMed Central, 2000 8(2007), 10 vom: 18. Okt. (DE-627)326173617 (DE-600)2040529-7 1474-760X nnns volume:8 year:2007 number:10 day:18 month:10 https://dx.doi.org/10.1186/gb-2007-8-10-r221 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2007 10 18 10
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This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">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. 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author	Coppin, Hélène
spellingShingle	Coppin, Hélène misc Iron Overload misc Additional Data File misc Iron Metabolism misc Hemochromatosis misc Hereditary Hemochromatosis 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
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topic_title	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 Iron Overload (dpeaa)DE-He213 Additional Data File (dpeaa)DE-He213 Iron Metabolism (dpeaa)DE-He213 Hemochromatosis (dpeaa)DE-He213 Hereditary Hemochromatosis (dpeaa)DE-He213
topic	misc Iron Overload misc Additional Data File misc Iron Metabolism misc Hemochromatosis misc Hereditary Hemochromatosis
topic_unstemmed	misc Iron Overload misc Additional Data File misc Iron Metabolism misc Hemochromatosis misc Hereditary Hemochromatosis
topic_browse	misc Iron Overload misc Additional Data File misc Iron Metabolism misc Hemochromatosis misc Hereditary Hemochromatosis
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title	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
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title_full	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
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author_browse	Coppin, Hélène Darnaud, Valérie Kautz, Léon Meynard, Delphine Aubry, Marc Mosser, Jean Martinez, Maria Roth, Marie-Paule
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title_sort	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
title_auth	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
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. © Coppin et al.; licensee BioMed Central Ltd. 2007. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (
abstractGer	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. © Coppin et al.; licensee BioMed Central Ltd. 2007. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (
abstract_unstemmed	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. © Coppin et al.; licensee BioMed Central Ltd. 2007. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (
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title_short	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
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This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">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.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Iron Overload</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Additional Data File</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Iron Metabolism</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Hemochromatosis</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Hereditary Hemochromatosis</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Darnaud, Valérie</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Kautz, Léon</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Meynard, Delphine</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Aubry, Marc</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Mosser, Jean</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Martinez, Maria</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Roth, Marie-Paule</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">Genome biology</subfield><subfield code="d">London : BioMed Central, 2000</subfield><subfield code="g">8(2007), 10 vom: 18. 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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

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