Basic ResearchInactivation of the hemochromatosis gene differentially regulates duodenal expression of iron-related mRNAs between mouse strains☆,☆☆,★,★★
Section snippets
Mice
The disrupted Hfe allele, initially on a mixed background (129/Ola × C57BL/6),3 was bred by successive crosses for 9 generations onto the DBA/2 and C57BL/6 backgrounds. Mice heterozygous for the disrupted allele were then mated to produce Hfe-null (Hfe−/−) mice. DBA/2 and C57BL/6 mice were purchased from the Centre d'Elevage Robert Janvier (Le Genest St-Isle, France) and used as wild-type (Hfe+/+) controls. The studied DBA/2 population consisted of 8 male and 8 female Hfe+/+ mice, and 12 male
Transferrin saturation and hepatic iron concentration in DBA/2 Hfe−/− mice
Twenty-three DBA/2 Hfe−/− mice and 16 Hfe+/+ mice of the same genetic background were analyzed at 6–7 weeks of age. Compared with the Hfe+/+ controls, the Hfe−/− mice had highly saturated serum transferrin levels (86.5% ± 2.2% vs. 45.9% ± 2.4%; P < 0.0001) and 6.4-fold higher levels of hepatic iron (2420 ± 155 vs. 377 ± 32 μg Fe/g dry liver; P < 0.0001) (Figure 1A).
Discussion
The up-regulation of the Dcytb (6.1-fold), DMT1 (5.1-fold), and FPN1 (2.3-fold) transcripts observed in the DBA/2 Hfe−/− mice relative to the Hfe+/+ mice of the same genetic background is reminiscent of the increase in expression of the Dcytb, DMT1 (≈15-fold each), and FPN1 (≈2.5-fold) transcripts observed in wild-type mice fed an iron-deficient diet for 2 weeks relative to control mice fed an iron-balanced diet (data submitted for publication). This up-regulation thus very much resembles the
Acknowledgements
The authors thank Michèle Stebenet (Service de Biochimie, Hôpital Purpan) for iron analyses, Janick Selves (Laboratoire d'Anatomie et Cytologie Pathologiques, Hôpital Purpan) for histologic assessment of liver iron deposition, Claudie Offer (Service Commun de Séquençage, IFR30) for sequencing of polymerase chain reaction products, and Maryline Calise (Service de Zootechnie, IFR30) for assistance in the mouse breedings.
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2009, Biochimica et Biophysica Acta - Molecular Basis of DiseaseBMP/Smad signaling is not enhanced in Hfe-deficient mice despite increased Bmp6 expression
2009, BloodCitation Excerpt :However, whether HFE when free of TFR1 has a role in the signaling cascade induced by the BMP6 ligand is still unknown. Our group has derived Hfe-deficient mice on different genetic backgrounds.21 These mice provide a unique opportunity to explore how Hfe deficiency affects the Bmp6/Smad signaling pathway in vivo.
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Address requests for reprints to: Marie-Paule Roth, M.D., UPCM, CNRS UPR 2163, CHU Purpan, 31059 Toulouse Cedex 3, France. e-mail: [email protected]; fax: (33) 5 6149 90 36.
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F.D. and S.F. contributed equally to this work.
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H.C. and M.-P.R. share senior authorship.
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Supported by EU (QLK6-CT-1999-02237) (Toulouse), INSERM-CreS and ACI Jeunes-Chercheurs-Ministère de la Recherche (Strasbourg). F.D. was supported by grants from the Fondation Danone and from ARC.