Long‐term sequelae of HFE deletion in C57BL/6 × 129/O1a mice, an animal model for hereditary haemochromatosis

Lebeau, Annette; Frank, Jürgen; Biesalski, H. K.; Weiss, Günter; Srai, Surjit Kaila; Simpson, Robert J.; McKie, Andrew T.; Bahram, Seiamak; Gilfillan, Susan; Schümann, Klaus

doi:10.1046/j.1365-2362.2002.01026.x

Cited by 30 publications

(31 citation statements)

References 34 publications

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“…Iron in internal organs of our animals showed differences between Hfe þ / þ mice and Hfe À/À mice as previously described in the literature (Levy et al, 1999;Lebeau et al, 2002;Turoczi et al, 2003). Iron in livers of 129/Sv Hfe À/À mice was 2-3-fold greater than iron in livers of 129/Sv Hfe þ / þ mice (Fig 1).…”

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confidence: 83%

Iron in Skin of Mice with Three Etiologies of Systemic Iron Overload

Adams

Lazova

Andrews

et al. 2005

Journal of Investigative Dermatology

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In human hemochromatosis, tissue toxicity is a function of tissue iron levels. Despite reports of skin toxicity in hemochromatosis, little is known about iron levels in skin of individuals with systemic iron overload. We measured skin iron and studied skin histology in three mouse models of systemic iron overload: mice with a deletion of the hemochromatosis (Hfe) gene, mice fed a high iron diet, and mice given parenteral injections of iron. In Hfe(-/-) mice, iron content in the epidermis and dermis was unexpectedly the same as in Hfe(+/+) mice, and there were no histological abnormalities detected after 30 wk. A high iron diet produced increased iron in the epidermis of both normal and Hfe(-/-) animals; a high diet increased iron in the dermis only in Hfe(-/-) mice. Increased skin iron was not associated with other histological changes, even after 19 wk. Parenteral administration of iron produced increased iron in the epidermis and dermis, and gave the skin a bronze hue. These results show that the amount and distribution of iron in the skin depends on the etiology of iron overload. It appears that neither Hfe deletion nor elevated skin iron alone can account for cutaneous manifestations reportedly seen in humans with hereditary hemochromatosis.

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supporting

confidence: 83%

Iron in Skin of Mice with Three Etiologies of Systemic Iron Overload

Adams

Lazova

Andrews

et al. 2005

Journal of Investigative Dermatology

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“…Iron absorption remains sufficiently well regulated in Hfe KO mice with this genetic background, so the high iron overload characteristic of human hemochromatosis is not seen in them. 17 This combined with the large variation seen in these animals (M.-P. Roth, personal communication, September 2002) is useful because it means that correlations can be informative with some overlap between the KO and wild-type genotype.…”

Section: Resultsmentioning

confidence: 99%

“…Hfe KO breeders (originally mixed 129/Ola-C57BL/6 background strain 4,17 ; donated by Susan Gilfillan, Department of Immunology, Washington University, St Louis, MO) were mated with C57BL/6 and subsequently genotyped by polymerase chain reaction (PCR). 4 Wild-type and Hfe KO homozygote breeders were established to produce age-matched male mice for experimental study.…”

Section: Methodsmentioning

confidence: 99%

Duodenal nonheme iron content correlates with iron stores in mice, but the relationship is altered by Hfe gene knock-out

Simpson

Debnam²,

Laftah³

et al. 2003

Blood

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Hereditary hemochromatosis is a common iron-loading disorder found in populations of European descent. It has been proposed that mutations causing loss of function of HFE gene result in reduced iron incorporation into immature duodenal crypt cells. These cells then overexpress genes for iron absorption, leading to inappropriate cellular iron balance, a persistent iron deficiency of the duodenal mucosa, and increased iron absorption. The objective was to measure duodenal iron content in Hfe knock-out mice to test whether the mutation causes a persistent decrease in enterocyte iron concentration. In both normal and Hfe knock-out mice, duodenal nonheme iron content was found to correlate with liver iron stores (P < .001, r ‫؍‬ 0.643 and 0.551, respectively), and this effect did not depend on dietary iron levels. However, duodenal iron content was reduced in Hfe knockout mice for any given content of liver iron stores (P < .001). (Blood. 2003;101: 3316-3318)

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“…3E). This contrasts with the persistent iron accumulation in aged HFEand Hamp-deficient animals (Nicolas et al, 2001;Lebeau et al, 2002;Nicolas et al, 2003). Importantly, chronic failure to induce Hamp expression in the context of iron overload has been shown to be the likely mechanism of dysregulated iron balance in HFE mutant mice (Ahmad et al, 2002;Nicolas et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Disruption of ferroportin 1 regulation causes dynamic alterations in iron homeostasis and erythropoiesis in polycythaemia mice

et al. 2004

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an erythropoietin (Epo)-dependent polycythemia in heterozygotes and a hypochromic, microcytic anemia in homozygotes. Interestingly, both defects in erythropoiesis were transient, correcting by young adulthood. Delayed upregulation of the negative hormonal regulator of iron homeostasis, hepcidin (Hamp), during postnatal development correlates strongly with profound increases in Fpn1 protein levels and polycythemia in Pcm heterozygotes. Thus, our data suggest that a Hampmediated regulatory interference alleviates the defects in iron homeostasis and transient alterations in erythropoiesis caused by a regulatory mutation in Fpn1.

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Long‐term sequelae of HFE deletion in C57BL/6 × 129/O1a mice, an animal model for hereditary haemochromatosis

Abstract: C57BL/6 x 129/O1a HFE(o/o) mice mimic HH iron distribution and the regulation of intestinal iron absorption after long-term feeding. However, characteristic morphological late changes in untreated HH are not modelled.

Cited by 30 publications

References 34 publications

Iron in Skin of Mice with Three Etiologies of Systemic Iron Overload

Iron in Skin of Mice with Three Etiologies of Systemic Iron Overload

Duodenal nonheme iron content correlates with iron stores in mice, but the relationship is altered by Hfe gene knock-out

Disruption of ferroportin 1 regulation causes dynamic alterations in iron homeostasis and erythropoiesis in polycythaemia mice

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