Hfe

Summary

Gene Symbol: Hfe
Description: hemochromatosis
Alias: MR2, hereditary hemochromatosis protein homolog
Species: mouse
Products:     Hfe

Top Publications

  1. Wallace D, Summerville L, Crampton E, Frazer D, Anderson G, Subramaniam V. Combined deletion of Hfe and transferrin receptor 2 in mice leads to marked dysregulation of hepcidin and iron overload. Hepatology. 2009;50:1992-2000 pubmed publisher
    Hepcidin is a central regulator of iron homeostasis. HFE and transferrin receptor 2 (TFR2) are mutated in adult-onset forms of hereditary hemochromatosis and regulate the expression of hepcidin in response to iron...
  2. Levy J, Montross L, Cohen D, Fleming M, Andrews N. The C282Y mutation causing hereditary hemochromatosis does not produce a null allele. Blood. 1999;94:9-11 pubmed
    Targeted mutagenesis was used to produce two mutations in the murine hemochromatosis gene (Hfe) locus. The first mutation deletes a large portion of the coding sequence, generating a null allele...
  3. Bahram S, Gilfillan S, Kuhn L, Moret R, Schulze J, Lebeau A, et al. Experimental hemochromatosis due to MHC class I HFE deficiency: immune status and iron metabolism. Proc Natl Acad Sci U S A. 1999;96:13312-7 pubmed
    ..linkage between genetic hemochromatosis and histocompatibility loci became even more so when the gene involved, HFE, was identified...
  4. Nairz M, Theurl I, Schroll A, Theurl M, Fritsche G, Lindner E, et al. Absence of functional Hfe protects mice from invasive Salmonella enterica serovar Typhimurium infection via induction of lipocalin-2. Blood. 2009;114:3642-51 pubmed publisher
    Mutations of HFE are associated with hereditary hemochromatosis, but their influence on host susceptibility to infection is incompletely understood...
  5. Wang L, Harrington L, Trebicka E, Shi H, Kagan J, Hong C, et al. Selective modulation of TLR4-activated inflammatory responses by altered iron homeostasis in mice. J Clin Invest. 2009;119:3322-8 pubmed publisher
    Mice deficient in the hemochromatosis gene, Hfe, have attenuated inflammatory responses to Salmonella infection associated with decreased macrophage TNF-alpha and IL-6 biosynthesis after exposure to LPS...
  6. Zhou X, Tomatsu S, Fleming R, Parkkila S, Waheed A, Jiang J, et al. HFE gene knockout produces mouse model of hereditary hemochromatosis. Proc Natl Acad Sci U S A. 1998;95:2492-7 pubmed
    ..Recently, a candidate gene for HH called HFE encoding a major histocompatibility complex class I-like protein was identified by positional cloning...
  7. Huang J, Gabrielsen J, Cooksey R, Luo B, Boros L, Jones D, et al. Increased glucose disposal and AMP-dependent kinase signaling in a mouse model of hemochromatosis. J Biol Chem. 2007;282:37501-7 pubmed
    ..despite decreased insulin secretion in a mouse model of hemochromatosis with deletion of the hemochromatosis gene (Hfe(-/-))...
  8. Gao J, Chen J, Kramer M, Tsukamoto H, Zhang A, Enns C. Interaction of the hereditary hemochromatosis protein HFE with transferrin receptor 2 is required for transferrin-induced hepcidin expression. Cell Metab. 2009;9:217-27 pubmed publisher
    ..with the most common form of hereditary iron overload have mutations in the hereditary hemochromatosis protein HFE. They have lower levels of hepcidin than unaffected individuals...
  9. Roy C, Custodio A, de Graaf J, Schneider S, Akpan I, Montross L, et al. An Hfe-dependent pathway mediates hyposideremia in response to lipopolysaccharide-induced inflammation in mice. Nat Genet. 2004;36:481-5 pubmed
    ..Mice with deficiencies in the hemochromatosis gene product, Hfe, mounted a general inflammatory response after injection of lipopolysaccharide but lacked appropriate Hamp ..

More Information

Publications86

  1. Abgueguen E, Toutain B, Bédrine H, Chicault C, Orhant M, Aubry M, et al. Differential expression of genes related to HFE and iron status in mouse duodenal epithelium. Mamm Genome. 2006;17:430-50 pubmed
    ..b>HFE, the hereditary hemochromatosis gene product, is expressed in the crypts of the duodenum, but the molecular ..
  2. Ajioka R, Levy J, Andrews N, Kushner J. Regulation of iron absorption in Hfe mutant mice. Blood. 2002;100:1465-9 pubmed
    ..is most commonly caused by homozygosity for a point mutation (C282Y) in the human hemochromatosis gene (HFE)...
  3. Trinder D, Olynyk J, Sly W, Morgan E. Iron uptake from plasma transferrin by the duodenum is impaired in the Hfe knockout mouse. Proc Natl Acad Sci U S A. 2002;99:5622-6 pubmed
    ..Most individuals with HH are homozygous for a C282Y mutation in the HFE gene...
  4. Wallace D, McDonald C, Ostini L, Subramaniam V. Blunted hepcidin response to inflammation in the absence of Hfe and transferrin receptor 2. Blood. 2011;117:2960-6 pubmed publisher
    ..b>Hfe and transferrin receptor 2 (Tfr2) are involved in the homeostatic regulation of hepcidin and their disruption ..
  5. Simpson R, Debnam E, Beaumont N, Bahram S, Schumann K, Srai S. Duodenal mucosal reductase in wild-type and Hfe knockout mice on iron adequate, iron deficient, and iron rich feeding. Gut. 2003;52:510-3 pubmed
    ..The disease is associated with loss of function mutations in the HFE gene. This is thought to change iron stores via increased iron absorption...
  6. Muckenthaler M, Roy C, Custodio A, Minana B, deGraaf J, Montross L, et al. Regulatory defects in liver and intestine implicate abnormal hepcidin and Cybrd1 expression in mouse hemochromatosis. Nat Genet. 2003;34:102-7 pubmed
    ..Most cases arise from a founder mutation in HFE (845G-->A; ref...
  7. Fleming R, Migas M, Zhou X, Jiang J, Britton R, Brunt E, et al. Mechanism of increased iron absorption in murine model of hereditary hemochromatosis: increased duodenal expression of the iron transporter DMT1. Proc Natl Acad Sci U S A. 1999;96:3143-8 pubmed
    ..We recently reported that HFE, the protein defective in HH, was physically associated with the transferrin receptor (TfR) in duodenal crypt cells ..
  8. Vujic Spasic M, Kiss J, Herrmann T, Galy B, Martinache S, Stolte J, et al. Hfe acts in hepatocytes to prevent hemochromatosis. Cell Metab. 2008;7:173-8 pubmed publisher
    ..In both humans and mice, type I HH is associated with mutations in the broadly expressed HFE/Hfe gene. To identify where Hfe acts to prevent HH, we generated mice with tissue-specific Hfe ablations...
  9. Turoczi T, Jun L, Cordis G, Morris J, Maulik N, Stevens R, et al. HFE mutation and dietary iron content interact to increase ischemia/reperfusion injury of the heart in mice. Circ Res. 2003;92:1240-6 pubmed
    ..To increase our understanding of the underlying pathogenic mechanisms of hereditary hemochromatosis, we used a HFE gene knockout mouse model that replicates hereditary hemochromatosis...
  10. Chaudhury C, Kim J, Mehnaz S, Wani M, Oberyszyn T, Bronson C, et al. Accelerated transferrin degradation in HFE-deficient mice is associated with increased transferrin saturation. J Nutr. 2006;136:2993-8 pubmed
    b>HFE, a major histocompatibility complex class I-related protein, is implicated in the iron overload disease, hereditary hemochromatosis...
  11. Vujic Spasic M, Kiss J, Herrmann T, Kessler R, Stolte J, Galy B, et al. Physiologic systemic iron metabolism in mice deficient for duodenal Hfe. Blood. 2007;109:4511-7 pubmed
    Mutations in the Hfe gene result in hereditary hemochromatosis (HH), a disorder characterized by increased duodenal iron absorption and tissue iron overload...
  12. Griffiths W, Sly W, Cox T. Intestinal iron uptake determined by divalent metal transporter is enhanced in HFE-deficient mice with hemochromatosis. Gastroenterology. 2001;120:1420-9 pubmed
    Overexpression of duodenal divalent metal transporter (DMT1) messenger RNA occurs in hemochromatosis and HFE-knockout mice, suggesting that DMT1 mediates enhanced absorption of iron; however, increased expression of functional DMT1 ..
  13. Wang L, Johnson E, Shi H, Walker W, Wessling Resnick M, Cherayil B. Attenuated inflammatory responses in hemochromatosis reveal a role for iron in the regulation of macrophage cytokine translation. J Immunol. 2008;181:2723-31 pubmed
    ..To study this phenomenon, we examined innate immunity to oral Salmonella infection in Hfe knockout (Hfe(-/-)) mice, a model of the human inherited disorder of iron metabolism type I hemochromatosis...
  14. Cooksey R, Jouihan H, Ajioka R, Hazel M, Jones D, Kushner J, et al. Oxidative stress, beta-cell apoptosis, and decreased insulin secretory capacity in mouse models of hemochromatosis. Endocrinology. 2004;145:5305-12 pubmed
    ..Mice with targeted deletion of the hemochromatosis gene (Hfe(-/-)) on the 129/Sv genetic background exhibited a 72% increase in iron content in the islets of Langerhans ..
  15. Ahmad K, Ahmann J, Migas M, Waheed A, Britton R, Bacon B, et al. Decreased liver hepcidin expression in the Hfe knockout mouse. Blood Cells Mol Dis. 2002;29:361-6 pubmed
    ..Transgenic mice lacking hepcidin expression demonstrate abnormalities of iron homeostasis similar to Hfe knockout mice and to patients with HFE-associated hereditary hemochromatosis (HH)...
  16. Herrmann T, Muckenthaler M, van der Hoeven F, Brennan K, Gehrke S, Hubert N, et al. Iron overload in adult Hfe-deficient mice independent of changes in the steady-state expression of the duodenal iron transporters DMT1 and Ireg1/ferroportin. J Mol Med (Berl). 2004;82:39-48 pubmed
    ..It has been hypothesized that mutations in the HH gene HFE cause misprogramming of the duodenal enterocytes towards a paradoxical iron-deficient state, resulting in increased ..
  17. Goswami T, Andrews N. Hereditary hemochromatosis protein, HFE, interaction with transferrin receptor 2 suggests a molecular mechanism for mammalian iron sensing. J Biol Chem. 2006;281:28494-8 pubmed
    b>HFE and transferrin receptor 2 (TFR2) are membrane proteins integral to mammalian iron homeostasis and associated with human hereditary hemochromatosis...
  18. Gorman N, Trask H, Bement W, Szakacs J, Elder G, Balestra D, et al. Genetic factors influence ethanol-induced uroporphyria in Hfe(-/-) mice. Hepatology. 2004;40:942-50 pubmed
    ..tarda (PCT) are alcohol consumption and homozygosity for the C282Y mutation in the hereditary hemochromatosis gene (HFE). We recently described an animal model for alcohol-induced uroporphyria, using Hfe(-/-) mice...
  19. Nandar W, Neely E, Unger E, Connor J. A mutation in the HFE gene is associated with altered brain iron profiles and increased oxidative stress in mice. Biochim Biophys Acta. 2013;1832:729-41 pubmed publisher
    Because of the increasing evidence that H63D HFE polymorphism appears in higher frequency in neurodegenerative diseases, we evaluated the neurological consequences of H63D HFE in vivo using mice that carry H67D HFE (homologous to human ..
  20. Vujic Spasic M, Sparla R, Mleczko Sanecka K, Migas M, Breitkopf Heinlein K, Dooley S, et al. Smad6 and Smad7 are co-regulated with hepcidin in mouse models of iron overload. Biochim Biophys Acta. 2013;1832:76-84 pubmed publisher
    ..Using mouse models for hereditary hemochromatosis (Hfe-, TfR2-, Hfe/TfR2-, Hjv- and hepcidin1-deficient mice) we show that hepcidin, Smad6 and Smad7 mRNA expression is ..
  21. Schmidt P, Toudjarska I, Sendamarai A, Racie T, Milstein S, Bettencourt B, et al. An RNAi therapeutic targeting Tmprss6 decreases iron overload in Hfe(-/-) mice and ameliorates anemia and iron overload in murine ?-thalassemia intermedia. Blood. 2013;121:1200-8 pubmed publisher
    Mutations in HFE lead to hereditary hemochromatosis (HH) because of inappropriately high iron uptake from the diet resulting from decreased hepatic expression of the iron-regulatory hormone hepcidin...
  22. Flanagan J, Peng H, Beutler E. Effects of alcohol consumption on iron metabolism in mice with hemochromatosis mutations. Alcohol Clin Exp Res. 2007;31:138-43 pubmed
    ..a major factor in expression of the hemochromatosis phenotype in patients homozygous for the C282Y mutation of the HFE gene...
  23. Kent P, Wilkinson N, Constante M, Fillebeen C, Gkouvatsos K, Wagner J, et al. Hfe and Hjv exhibit overlapping functions for iron signaling to hepcidin. J Mol Med (Berl). 2015;93:489-98 pubmed publisher
    Functional inactivation of HFE or hemojuvelin (HJV) is causatively linked to adult or juvenile hereditary hemochromatosis, respectively. Systemic iron overload results from inadequate expression of hepcidin, the iron regulatory hormone...
  24. Lunova M, Schwarz P, Nuraldeen R, Levada K, Kuscuoglu D, Stützle M, et al. Hepcidin knockout mice spontaneously develop chronic pancreatitis owing to cytoplasmic iron overload in acinar cells. J Pathol. 2017;241:104-114 pubmed publisher
    ..Hepcidin and Hfe KO mice were compared with wild-type (WT) mice kept on standard or iron-rich diets...
  25. Hall E, Lee S, Simmons Z, Neely E, Nandar W, Connor J. Prolyl-peptidyl isomerase, Pin1, phosphorylation is compromised in association with the expression of the HFE polymorphic allele, H63D. Biochim Biophys Acta. 2010;1802:389-95 pubmed publisher
    There is substantial interest in HFE gene variants as putative risk factors in neurodegenerative diseases such as Alzheimer disease (AD)...
  26. Finberg K, Whittlesey R, Andrews N. Tmprss6 is a genetic modifier of the Hfe-hemochromatosis phenotype in mice. Blood. 2011;117:4590-9 pubmed publisher
    The hereditary hemochromatosis protein HFE promotes the expression of hepcidin, a circulating hormone produced by the liver that inhibits dietary iron absorption and macrophage iron release...
  27. Layoun A, Huang H, Calvé A, Santos M. Toll-like receptor signal adaptor protein MyD88 is required for sustained endotoxin-induced acute hypoferremic response in mice. Am J Pathol. 2012;180:2340-50 pubmed publisher
    ..through LPS and polyinosinic:polycytidylic acid [poly(I:C)] treatments resulted in rapid down-regulation of HFE protein [encoded by the hemochromatosis gene (Hfe)] and ferroportin [encoded by solute carrier family 40 (iron-..
  28. Magens B, Düllmann J, Schümann K, Wulfhekel U, Nielsen P. Nuclear iron deposits in hepatocytes of iron-loaded HFE-knock-out mice: a morphometric and immunocytochemical analysis. Acta Histochem. 2005;107:57-65 pubmed
    ..Animals with no, partial or total knock-out of the HFE alleles, the deletion of which is responsible for hereditary haemochromatosis, were given different forms of ..
  29. Fleming R, Holden C, Tomatsu S, Waheed A, Brunt E, Britton R, et al. Mouse strain differences determine severity of iron accumulation in Hfe knockout model of hereditary hemochromatosis. Proc Natl Acad Sci U S A. 2001;98:2707-11 pubmed
    Hereditary hemochromatosis (HH) is a common disorder of iron metabolism caused by mutation in HFE, a gene encoding an MHC class I-like protein...
  30. Gunshin H, Fujiwara Y, Custodio A, Direnzo C, Robine S, Andrews N. Slc11a2 is required for intestinal iron absorption and erythropoiesis but dispensable in placenta and liver. J Clin Invest. 2005;115:1258-66 pubmed
    ..We previously showed that Slc11a2 serves as the primary portal for intestinal iron entry in hemochromatosis. However, inactivation of murine Hfe ameliorates the phenotype of animals lacking Slc11a2.
  31. Rishi G, Crampton E, Wallace D, Subramaniam V. In situ proximity ligation assays indicate that hemochromatosis proteins Hfe and transferrin receptor 2 (Tfr2) do not interact. PLoS ONE. 2013;8:e77267 pubmed publisher
    The hemochromatosis associated proteins HFE and Transferrin Receptor 2 (TFR2) have been shown to be important for the proper regulation of hepcidin...
  32. Heritage M, Murphy T, Bridle K, Anderson G, Crawford D, Fletcher L. Hepcidin regulation in wild-type and Hfe knockout mice in response to alcohol consumption: evidence for an alcohol-induced hypoxic response. Alcohol Clin Exp Res. 2009;33:1391-400 pubmed publisher
    Expression of Hamp1, the gene encoding the iron regulatory peptide hepcidin, is inappropriately low in HFE-associated hereditary hemochromatosis and Hfe knockout mice (Hfe(-/-))...
  33. Fleming R, Migas M, Holden C, Waheed A, Britton R, Tomatsu S, et al. Transferrin receptor 2: continued expression in mouse liver in the face of iron overload and in hereditary hemochromatosis. Proc Natl Acad Sci U S A. 2000;97:2214-9 pubmed
    ..of dietary iron overload (2% carbonyl iron), dietary iron deficiency (gastric parietal cell ablation), and HH (HFE -/-)...
  34. Castoldi M, Vujic Spasic M, Altamura S, Elmen J, Lindow M, Kiss J, et al. The liver-specific microRNA miR-122 controls systemic iron homeostasis in mice. J Clin Invest. 2011;121:1386-96 pubmed publisher
    ..increased the amount of mRNA transcribed by genes that control systemic iron levels, such as hemochromatosis (Hfe), hemojuvelin (Hjv), bone morphogenetic protein receptor type 1A (Bmpr1a), and Hamp...
  35. Constante M, Wang D, Raymond V, Bilodeau M, Santos M. Repression of repulsive guidance molecule C during inflammation is independent of Hfe and involves tumor necrosis factor-alpha. Am J Pathol. 2007;170:497-504 pubmed
    Genetic iron overload, or hemochromatosis, can be caused by mutations in HFE, hemojuvelin, and hepcidin genes...
  36. Britton L, Jaskowski L, Bridle K, Santrampurwala N, Reiling J, Musgrave N, et al. Heterozygous Hfe gene deletion leads to impaired glucose homeostasis, but not liver injury in mice fed a high-calorie diet. Physiol Rep. 2016;4: pubmed publisher
    Heterozygous mutations of the Hfe gene have been proposed as cofactors in the development and progression of nonalcoholic fatty liver disease (NAFLD)...
  37. Johnstone D, Graham R, Trinder D, Delima R, Riveros C, Olynyk J, et al. Brain transcriptome perturbations in the Hfe(-/-) mouse model of genetic iron loading. Brain Res. 2012;1448:144-52 pubmed publisher
    ..disorders such as hereditary hemochromatosis, which is usually caused by loss-of-function polymorphisms in the HFE gene...
  38. Kielmanowicz M, Laham N, Coligan J, Lemonnier F, Ehrlich R. Mouse HFE inhibits Tf-uptake and iron accumulation but induces non-transferrin bound iron (NTBI)-uptake in transformed mouse fibroblasts. J Cell Physiol. 2005;202:105-14 pubmed
    ..A non-classical class I MHC molecule, the hemochromatosis factor (HFE), has been shown to regulate iron metabolism, potentially via its interaction with the transferrin receptor...
  39. Santos M, Miranda C, Levy J, Montross L, Cossee M, Sequeiros J, et al. Iron metabolism in mice with partial frataxin deficiency. Cerebellum. 2003;2:146-53 pubmed
    ..frataxin deficiency on susceptibility to cardiac damage in the mouse model of hereditary hemochromatosis (HH), the Hfe knockout mice...
  40. Knutson M, Levy J, Andrews N, Wessling Resnick M. Expression of stimulator of Fe transport is not enhanced in Hfe knockout mice. J Nutr. 2001;131:1459-64 pubmed
    b>Hfe knockout (-/-) mice recapitulate many of the biochemical abnormalities of hereditary hemochromatosis (HH), but the molecular mechanisms involved in the etiology of iron overload in HH remain poorly understood...
  41. Bettencourt C, Forabosco P, Wiethoff S, Heidari M, Johnstone D, Botía J, et al. Gene co-expression networks shed light into diseases of brain iron accumulation. Neurobiol Dis. 2016;87:59-68 pubmed publisher
    ..Our results are of further relevance for these diseases by providing candidates for new causative genes and possible points for therapeutic intervention. ..
  42. Gutierrez L, Quintana C, Patiño C, Bueno J, Coppin H, Roth M, et al. Iron speciation study in Hfe knockout mice tissues: magnetic and ultrastructural characterisation. Biochim Biophys Acta. 2009;1792:541-7 pubmed publisher
    Liver, spleen and heart tissues of DBA/2 Hfe knockout mice have been characterised by low temperature AC magnetic susceptibility measurements together with Transmission Electron Microscopy (TEM) and Selected Area Electron Diffraction in ..
  43. Gnana Prakasam J, Thangaraju M, Liu K, Ha Y, Martin P, Smith S, et al. Absence of iron-regulatory protein Hfe results in hyperproliferation of retinal pigment epithelium: role of cystine/glutamate exchanger. Biochem J. 2009;424:243-52 pubmed publisher
    ..Mutations in HFE (histocompatability leucocyte antigen class I-like protein involved in iron homoeostasis) are responsible for most ..
  44. Arkell R, Cadman M, Marsland T, Southwell A, Thaung C, Davies J, et al. Genetic, physical, and phenotypic characterization of the Del(13)Svea36H mouse. Mamm Genome. 2001;12:687-94 pubmed
    ..Both the heterozygous viability and the penetrance of the visible phenotypes vary with genetic background. ..
  45. Miranda C, Makui H, Andrews N, Santos M. Contributions of beta2-microglobulin-dependent molecules and lymphocytes to iron regulation: insights from HfeRag1(-/-) and beta2mRag1(-/-) double knock-out mice. Blood. 2004;103:2847-9 pubmed
    Genetic causes of hereditary hemochromatosis (HH) include mutations in the HFE gene, coding for a beta2-microglobulin (beta2m)-associated major histocompatibility complex class I-like protein...
  46. Riegert P, Gilfillan S, Nanda I, Schmid M, Bahram S. The mouse HFE gene. Immunogenetics. 1998;47:174-7 pubmed
  47. Simpson R, Debnam E, Laftah A, Solanky N, Beaumont N, Bahram S, et al. Duodenal nonheme iron content correlates with iron stores in mice, but the relationship is altered by Hfe gene knock-out. Blood. 2003;101:3316-8 pubmed
    ..It has been proposed that mutations causing loss of function of HFE gene result in reduced iron incorporation into immature duodenal crypt cells...
  48. Wu Q, Wang H, An P, Tao Y, Deng J, Zhang Z, et al. HJV and HFE Play Distinct Roles in Regulating Hepcidin. Antioxid Redox Signal. 2015;22:1325-36 pubmed publisher
    Hereditary hemochromatosis (HH) is an iron overload disease that is caused by mutations in HFE, HJV, and several other genes. However, whether HFE-HH and HJV-HH share a common pathway via hepcidin regulation is currently unclear...
  49. Makui H, Soares R, Jiang W, Constante M, Santos M. Contribution of Hfe expression in macrophages to the regulation of hepatic hepcidin levels and iron loading. Blood. 2005;106:2189-95 pubmed
    Hereditary hemochromatosis (HH), an iron overload disease associated with mutations in the HFE gene, is characterized by increased intestinal iron absorption and consequent deposition of excess iron, primarily in the liver...
  50. Simpson R, Deenmamode J, McKie A, Raja K, Salisbury J, Iancu T, et al. Time-course of iron overload and biochemical, histopathological and ultrastructural evidence of pancreatic damage in hypotransferrinaemic mice. Clin Sci (Lond). 1997;93:453-62 pubmed
    ..The hypotransferrinaemic mouse pancreas is a useful model system for investigation of parenchymal cell damage by iron. ..
  51. Wilkin R, Lalor P, Parker R, Newsome P. Murine Models of Acute Alcoholic Hepatitis and Their Relevance to Human Disease. Am J Pathol. 2016;186:748-60 pubmed publisher
  52. Delima R, Chua A, Tirnitz Parker J, Gan E, Croft K, Graham R, et al. Disruption of hemochromatosis protein and transferrin receptor 2 causes iron-induced liver injury in mice. Hepatology. 2012;56:585-93 pubmed publisher
    Mutations in hemochromatosis protein (HFE) or transferrin receptor 2 (TFR2) cause hereditary hemochromatosis (HH) by impeding production of the liver iron-regulatory hormone, hepcidin (HAMP)...
  53. Gnana Prakasam J, Martin P, Mysona B, Roon P, Smith S, Ganapathy V. Hepcidin expression in mouse retina and its regulation via lipopolysaccharide/Toll-like receptor-4 pathway independent of Hfe. Biochem J. 2008;411:79-88 pubmed
    ..The upregulation of hepcidin by LPS occurs independent of Hfe (human leukocyte antigen-like protein involved in Fe homeostasis)...
  54. Sinclair P, Gorman N, Trask H, Bement W, Szakacs J, Elder G, et al. Uroporphyria caused by ethanol in Hfe(-/-) mice as a model for porphyria cutanea tarda. Hepatology. 2003;37:351-8 pubmed
    ..tarda (PCT) are alcohol consumption and homozygosity for the C282Y mutation in the hereditary hemochromatosis gene (HFE). To develop an animal model, Hfe knockout mice were treated continuously with 10% ethanol in drinking water...
  55. Bensaid M, Fruchon S, Mazères C, Bahram S, Roth M, Coppin H. Multigenic control of hepatic iron loading in a murine model of hemochromatosis. Gastroenterology. 2004;126:1400-8 pubmed
    ..Most patients are homozygous for the C282Y mutation in the HFE gene...
  56. Smith K, Kovac S, Anderson G, Shulkes A, Baldwin G. Circulating gastrin is increased in hemochromatosis. FEBS Lett. 2006;580:6195-8 pubmed
    ..Gastrin concentrations are increased in the plasma and gastric mucosa of Hfe(-/-) mice, and in the sera of humans with HFE-related hemochromatosis...
  57. Poli M, Luscieti S, Gandini V, Maccarinelli F, Finazzi D, Silvestri L, et al. Transferrin receptor 2 and HFE regulate furin expression via mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/Erk) signaling. Implications for transferrin-dependent hepcidin regulation. Haematologica. 2010;95:1832-40 pubmed publisher
    ..regulation of hepcidin in response to iron is the cause of genetic hemochromatosis associated with defects of HFE and transferrin receptor 2. However, the role of these proteins in the regulation of hepcidin expression is unclear...
  58. Dupic F, Fruchon S, Bensaid M, Borot N, Radosavljevic M, Loreal O, et al. Inactivation of the hemochromatosis gene differentially regulates duodenal expression of iron-related mRNAs between mouse strains. Gastroenterology. 2002;122:745-51 pubmed
    b>Hfe knockout mice, like patients with hereditary hemochromatosis, have augmented duodenal iron absorption and increased iron deposition in hepatic parenchymal cells...
  59. Boucherma R, Kridane Miledi H, Vives F, Vauchy C, Borg C, Kleinclauss F, et al. Loss of central and peripheral CD8+ T-cell tolerance to HFE in mouse models of human familial hemochromatosis. Eur J Immunol. 2012;42:851-62 pubmed publisher
    b>HFE, an MHC class Ib molecule that controls iron metabolism, can be directly targeted by cytotoxic TCR ?? T lymphocytes...
  60. Lee P, Peng H, Gelbart T, Beutler E. The IL-6- and lipopolysaccharide-induced transcription of hepcidin in HFE-, transferrin receptor 2-, and beta 2-microglobulin-deficient hepatocytes. Proc Natl Acad Sci U S A. 2004;101:9263-5 pubmed
    ..Studies in humans and mice have shown that this iron-dependent pathway requires the presence of Hfe, hemojuvelin, and probably transferrin receptor 2 (tfr-2)...
  61. Hughes A, Yeager M, Ten Elshof A, Chorney M. A new taxonomy of mammalian MHC class I molecules. Immunol Today. 1999;20:22-6 pubmed
  62. Aksu S, Koczan D, Renne U, Thiesen H, Brockmann G. Differentially expressed genes in adipose tissues of high body weight-selected (obese) and unselected (lean) mouse lines. J Appl Genet. 2007;48:133-43 pubmed
    ..14 out of these genes, occur in QTL regions for body weight or abdominal fat weight. Further analyses are necessary to discriminate between genes directly causing QTL effects and indirectly regulated differentially expressed genes. ..
  63. Gomes Pereira S, Rodrigues P, Appelberg R, Gomes M. Increased susceptibility to Mycobacterium avium in hemochromatosis protein HFE-deficient mice. Infect Immun. 2008;76:4713-9 pubmed publisher
    ..cells, mainly in the liver, and is most often associated with mutations in the gene encoding the molecule HFE. In this paper, we demonstrate that mice of two genetically determined primary iron overload phenotypes, Hfe(-/-) ..
  64. Fergelot P, Ropert Bouchet M, Abgueguen E, Orhant M, Radosavljevic M, Grimber G, et al. Iron overload in mice expressing HFE exclusively in the intestinal villi provides evidence that HFE regulates a functional cross-talk between crypt and villi enterocytes. Blood Cells Mol Dis. 2002;28:348-60 pubmed
    Hereditary hemochromatosis (HH), a common autosomal recessive disorder due to a mutation in HFE, which encodes an atypical MHC class I glycoprotein, is characterized by excessive absorption of dietary iron...
  65. Shen J, Sheng X, Chang Z, Wu Q, Wang S, Xuan Z, et al. Iron metabolism regulates p53 signaling through direct heme-p53 interaction and modulation of p53 localization, stability, and function. Cell Rep. 2014;7:180-93 pubmed publisher
  66. Huang J, Jones D, Luo B, Sanderson M, Soto J, Abel E, et al. Iron overload and diabetes risk: a shift from glucose to Fatty Acid oxidation and increased hepatic glucose production in a mouse model of hereditary hemochromatosis. Diabetes. 2011;60:80-7 pubmed publisher
    ..in vivo and in vitro in a mouse model of hemochromatosis in which the gene most often mutated in the human disease, HFE, has been deleted (Hfe?(/)?)...
  67. Gouya L, Muzeau F, Robreau A, Letteron P, Couchi E, Lyoumi S, et al. Genetic study of variation in normal mouse iron homeostasis reveals ceruloplasmin as an HFE-hemochromatosis modifier gene. Gastroenterology. 2007;132:679-86 pubmed
    ..European populations, genetic hemochromatosis is usually caused by homozygosity for the C282Y mutation in the HFE protein...
  68. Johnstone D, Graham R, Trinder D, Riveros C, Olynyk J, Scott R, et al. Changes in brain transcripts related to Alzheimer's disease in a model of HFE hemochromatosis are not consistent with increased Alzheimer's disease risk. J Alzheimers Dis. 2012;30:791-803 pubmed publisher
    ..used microarrays and real-time reverse transcription-PCR to investigate changes in the brain transcriptome of adult Hfe-/- mice, a model of hemochromatosis, relative to age- and gender-matched wildtype controls...
  69. Lee S, Connor J. Regulation of Hfe by stress factors in BV-2 cells. Neurobiol Aging. 2005;26:803-12 pubmed
    Mutations in the Hfe gene can be associated with the iron overload disorder known as hemochromatosis. A number of recent studies suggest that carrying an Hfe mutation is a risk factor or genetic modifier for Alzheimer's disease (AD)...
  70. Constante M, Jiang W, Wang D, Raymond V, Bilodeau M, Santos M. Distinct requirements for Hfe in basal and induced hepcidin levels in iron overload and inflammation. Am J Physiol Gastrointest Liver Physiol. 2006;291:G229-37 pubmed
    ..Hereditary hemochromatosis patients and Hfe-deficient mice show inappropriate expression of hepcidin but, in apparent contradiction, still retain the ability ..
  71. Hashimoto K, Hirai M, Kurosawa Y. Identification of a mouse homolog for the human hereditary haemochromatosis candidate gene. Biochem Biophys Res Commun. 1997;230:35-9 pubmed
    ..we have isolated this gene in the course of a search for new human MHC class I-related genes and named it MR2. Here we report a mouse homolog of this human gene...
  72. Tolosano E, Fagoonee S, Garuti C, Valli L, Andrews N, Altruda F, et al. Haptoglobin modifies the hemochromatosis phenotype in mice. Blood. 2005;105:3353-5 pubmed
    Classic hereditary hemochromatosis (HH) is a common genetic disorder of iron metabolism caused by a mutation in the HFE gene...
  73. Tan T, Crawford D, Jaskowski L, Murphy T, Heritage M, Subramaniam V, et al. Altered lipid metabolism in Hfe-knockout mice promotes severe NAFLD and early fibrosis. Am J Physiol Gastrointest Liver Physiol. 2011;301:G865-76 pubmed publisher
    The HFE protein plays a crucial role in the control of cellular iron homeostasis. Steatosis is commonly observed in HFE-related iron-overload disorders, and current evidence suggests a causal link between iron and steatosis...
  74. Guo S, Casu C, Gardenghi S, Booten S, Aghajan M, Peralta R, et al. Reducing TMPRSS6 ameliorates hemochromatosis and ?-thalassemia in mice. J Clin Invest. 2013;123:1531-41 pubmed publisher
    Thalassemia and HFE-related hemochromatosis are 2 of the most frequently inherited disorders worldwide. Both disorders are characterized by low levels of hepcidin (HAMP), the hormone that regulates iron absorption...
  75. Nandar W, Neely E, Simmons Z, Connor J. H63D HFE genotype accelerates disease progression in animal models of amyotrophic lateral sclerosis. Biochim Biophys Acta. 2014;1842:2413-26 pubmed publisher
    H63D HFE is associated with iron dyshomeostasis and oxidative stress; each of which plays an important role in amyotrophic lateral sclerosis (ALS) pathogenesis...
  76. Wilkins S, Frazer D, Millard K, McLaren G, Anderson G. Iron metabolism in the hemoglobin-deficit mouse: correlation of diferric transferrin with hepcidin expression. Blood. 2006;107:1659-64 pubmed
    ..These data strengthen the proposal that diferric transferrin is a key indicator of body iron requirements. ..
  77. Barasch J, Hollmén M, Deng R, Hod E, Rupert P, Abergel R, et al. Disposal of iron by a mutant form of lipocalin 2. Nat Commun. 2016;7:12973 pubmed publisher
    ..iron from iron overloaded mice, including models of acquired (iron-dextran or stored red blood cells) and primary (Hfe-/-) iron overload. In each case, the mutants reduce redox activity typical of non-transferrin-bound iron...