Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Iron homeostasis: insights from genetics and animal models

Nature Reviews Genetics volume 1, pages 208–217 (2000)Cite this article

Key Points

  • Iron balance must be strictly maintained to ensure that adequate amounts of iron are available for vital functions and to avoid the toxicity that results from iron excess. Disorders of iron deficiency and iron overload develop when iron balance is disrupted.

  • Iron is absorbed by enterocytes in the proximal intestine; it is stored in hepatocytes, used primarily by erythroid cells, and is recycled by specialized macrophages. There are similarities in the iron-transport strategies used by these different cell types, but tissue-specific differences also exist.

  • Two iron transporters, DMT1 (an importer) and ferroportin1 (an exporter — also known as Ireg1 or MTP1), have been identified by positional cloning.

  • Targeted mutagenesis has produced new mouse models of human iron disorders, including models for hereditary haemochromatosis and aceruloplasminaemia.

  • Despite recent advances in our understanding of iron absorption and iron recycling, many mechanistic details remain to be understood.

Abstract

Disorders that perturb iron balance are among the most prevalent human diseases, but until recently iron transport remained poorly understood. Over the past five years, genetic studies of patients with inherited iron homeostasis disorders and the analysis of mutant mice, rats and zebrafish have helped to identify several important iron-transport proteins. With information being mined from the genomes of four species, the study of iron metabolism has benefited enormously from positional-cloning efforts. Complementing the genomic strategy, targeted mutagenesis in mice has produced new models of human iron diseases. The animal models described in this review offer valuable tools for investigating iron homeostasis in vivo.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Distribution of iron within the body.
Figure 2: The transferrin cycle.
Figure 3: Cellular iron transport.

Similar content being viewed by others

References

  1. Finch, C. Regulators of iron balance in humans. Blood 84, 1697–1702 (1994).

    CAS  PubMed  Google Scholar 

  2. Andrews, N. C. & Fleming, M. D. Commentary on: ferrokinetics in the syndrome of familial hypoferremic microcytic anemia with iron malabsorption . J. Pediatr. Hematol. Oncol. 21, 353– 355 (1999).

    Article  CAS  PubMed  Google Scholar 

  3. Buchanan, G. R. & Sheehan, R. G. Malabsorption and defective utilization of iron in three siblings. J. Pediatr. 98, 723–728 ( 1981).

    Article  CAS  PubMed  Google Scholar 

  4. Hartman, K. R. & Barker, J. A. Microcytic anemia with iron malabsorption: An inherited disorder of iron metabolism. Am. J. Hematol. 51, 269–275 (1996).

    Article  CAS  PubMed  Google Scholar 

  5. Pearson, H. A. & Lukens, J. N. Ferrokinetics in the syndrome of familial hypoferremic microcytic anemia with iron malabsorption. J. Pediatr. Hematol. Oncol. 21, 412– 417 (1999).

    Article  CAS  PubMed  Google Scholar 

  6. Schade, A. L. & Caroline, L. An iron-binding component in human blood plasma. Science 104, 340– 341 (1946).

    Article  CAS  PubMed  Google Scholar 

  7. Bannerman, R. M. Genetic defects of iron transport. Fed. Proc. 35, 2281 (1976).

    CAS  PubMed  Google Scholar 

  8. Bernstein, S. E. Hereditary hypotransferrinemia with hemosiderosis, a murine disorder resembling human atransferrinemia. J. Lab. Clin. Med. 110, 690–705 (1987).

    CAS  PubMed  Google Scholar 

  9. Huggenvik, J. I. et al. A splicing defect in the mouse transferrin gene leads to congenital atransferrinemia. Blood 74, 482– 486 (1989).

    CAS  PubMed  Google Scholar 

  10. Trenor, C. C., Campagna, D. R., Sellers, V. M., Andrews, N. C. & Fleming, M. D. The molecular defect in hypotransferrinemic mice. Blood 96, 1113–1118 (2000).

    CAS  PubMed  Google Scholar 

  11. Kaplan, J. et al. Regulation of the distribution of tissue iron. Lessons learned from the hypotransferrinemic mouse. Ann. NY Acad. Sci. 526, 124–135 (1988).

    Article  CAS  PubMed  Google Scholar 

  12. Simpson, R. J. et al. Tissue iron loading and histopathological changes in hypotransferrinaemic mice. J. Pathol. 171, 237– 244 (1993).

    Article  CAS  PubMed  Google Scholar 

  13. Heilmeyer, L. et al. Congenital transferrin deficiency in a seven-year old girl . German Med. Mon. 86, 1745– 1751 (1961).

    CAS  Google Scholar 

  14. Goya, N., Miyazaki, S., Kodate, S. & Ushio, B. A family of congenital atransferrinemia. Blood 40, 239– 245 (1972).

    CAS  PubMed  Google Scholar 

  15. Hamill, R. L., Woods, J. C. & Cook, B. A. Congenital atransferrinemia: a case report and review of the literature. Am. J. Clin. Pathol. 96, 215–218 (1991).

    Article  CAS  PubMed  Google Scholar 

  16. Russell, E. S., McFarland, E. C. & Kent, E. L. Low viability, skin lesions, and reduced fertility associated with microcytic anemia in the mouse. Transpl. Proc. 2, 144–151 ( 1970).

    CAS  Google Scholar 

  17. Edwards, J. A. & Hoke, J. E. Defect of intestinal mucosal iron uptake in mice with hereditary microcytic anemia. Proc. Soc. Exp. Biol. Med. 141, 81– 84 (1972).

    Article  CAS  PubMed  Google Scholar 

  18. Riedel, H. D., Remus, A. J., Fitscher, B. A. & Stremmel, W. Characterization and partial purification of a ferrireductase from human duodenal microvillus membranes. Biochem. J. 309, 745–748 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Edwards, J. A. & Hoke, J. E. Red cell iron uptake in hereditary microcytic anemia. Blood 46, 381–388 (1975).

    CAS  PubMed  Google Scholar 

  20. Harrison, D. E. Marrow transplantation and iron therapy in mouse hereditary microcytic anemia . Blood 40, 893–901 (1972).

    CAS  PubMed  Google Scholar 

  21. Fleming, M. D. et al. Microcytic anemia mice have a mutation in Nramp2, a candidate iron transporter gene. Nature Genet. 16, 383–386 (1997).Provided the first evidence that Nramp2 (the gene encoding DMT1) is mutated in mk mice and is a major intestinal iron transporter.

    Article  CAS  PubMed  Google Scholar 

  22. Supek, F., Supekova, L., Nelson, H. & Nelson, N. A yeast manganese transporter related to the macrophage protein involved in conferring resistance to mycobacteria. Proc. Natl Acad. Sci. USA 93, 5105–5110 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Gunshin, H. et al. Cloning and characterization of a mammalian proton-coupled metal-ion transporter. Nature 388, 482– 488 (1997).DMT1 (termed DCT1 in this study) was isolated by expression cloning in Xenopus oocytes and shown to transport ferrous iron and other divalent metal ions.

    Article  CAS  PubMed  Google Scholar 

  24. Su, M. A., Trenor, C. C., Fleming, J. C., Fleming, M. D. & Andrews, N. C. The G185R mutation disrupts function of iron transporter Nramp2. Blood 92, 2157 –2163 (1998).

    CAS  PubMed  Google Scholar 

  25. Canonne-Hergaux, F. et al. The NRAMP2/DMT1 iron transporter is induced in the duodenum of microcytic anemia mk mice but is not properly targeted to the intestinal brush border. Blood (in the press).

  26. Oates, P. S. & Morgan, E. H. Defective iron uptake by the duodenum of Belgrade rats fed diets of different iron contents. Am. J. Physiol. 270, G826–G832 ( 1996).

    CAS  PubMed  Google Scholar 

  27. Sladic-Simic, D. et al. A thalassemia-like disorder in Belgrade laboratory rats. Ann. NY Acad. Sci. 165, 93–99 (1969).

    Article  CAS  PubMed  Google Scholar 

  28. Bowen, B. J. & Morgan, E. H. Anemia of the Belgrade rat: evidence for defective membrane transport of iron. Blood 70, 38–44 (1987).

    CAS  PubMed  Google Scholar 

  29. Edwards, J., Huebers, H., Kunzler, C. & Finch, C. Iron metabolism in the Belgrade rat. Blood 67, 623– 628 (1986).

    CAS  PubMed  Google Scholar 

  30. Fleming, M. D. et al. Nramp2 is mutated in the anemic Belgrade (b) rat: evidence of a role for Nramp2 in endosomal iron transport. Proc. Natl Acad. Sci. USA 95, 1148–1153 ( 1998).By identifying a mutation in the b rat, DMT1 was shown to transport iron into and out of endosomes.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Canonne-Hergaux, F., Gruenheid, S., Ponka, P. & Gros, P. Cellular and subcellular localization of the Nramp2 iron transporter in the intestinal brush border and regulation by dietary iron. Blood 93, 4406–4417 (1999).

    CAS  PubMed  Google Scholar 

  32. Gruenheid, S. et al. The iron transport protein NRAMP2 is an integral membrane glycoprotein that co-localizes with transferrin in recycling endosomes. J. Exp. Med. 189, 831–841 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Farcich, E. A. & Morgan, E. H. Diminished iron acquisition by cells and tissues of Belgrade laboratory rats. Am. J. Physiol. 262, R220–R224 (1992).

    CAS  PubMed  Google Scholar 

  34. Rodrigues, V., Cheah, P. Y., Ray, K. & Chia, W. malvolio, the Drosophila homologue of mouse NRAMP–1 (Bcg), is expressed in macrophages and in the nervous system and is required for normal taste behaviour. EMBO J. 14, 3007– 3020 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Orgad, S., Nelson, H., Segal, D. & Nelson, N. Metal ions suppress the abnormal taste behaviour of the Drosophila mutant malvolio. J. Exp. Biol. 201, 115–120 (1998).

    CAS  PubMed  Google Scholar 

  36. Haffter, P. et al. The identification of genes with unique and essential functions in the development of the zebrafish, Danio rerio. Development 123, 1–36 ( 1996).

    CAS  PubMed  Google Scholar 

  37. Kingston, P. J., Bannerman, C. E. & Bannerman, R. M. Iron deficiency anaemia in newborn sla mice: a genetic defect of placental iron transport. Br. J. Haematol. 40, 265–276 ( 1978).

    Article  CAS  PubMed  Google Scholar 

  38. Edwards, J. A. & Bannerman, R. M. Hereditary defect of intestinal iron transport in mice with sex-linked anemia. J. Clin. Invest. 49, 1869–1871 (1970).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Pinkerton, P. H., Bannerman, R. M., Doeblin, T. D., Benisch, B. M. & Edwards, J. A. Iron metabolism and absorption studies in the X-linked anaemia of mice. Br. J. Haematol. 18, 211–228 (1970).

    Article  CAS  PubMed  Google Scholar 

  40. Vulpe, C. D. et al. Hephaestin, a ceruloplasmin homologue implicated in intestinal iron transport, is defective in the sla mouse. Nature Genet. 21, 195–199 ( 1999).Showed that hephaestin is mutated in sla mice and is involved in intestinal iron transport.

    Article  CAS  PubMed  Google Scholar 

  41. Donovan, A. et al. Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter. Nature 403, 776–781 (2000).Reported the positional cloning of the first vertebrate iron exporter, ferroportin1/IREG1/MTP1.

    Article  CAS  PubMed  Google Scholar 

  42. McKie, A. T. et al. A novel duodenal iron-regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation. Mol. Cell 5, 299–309 ( 2000).In this study, ferroportin1/IREG1/MTP1 was isolated by differential expression analysis.

    Article  CAS  PubMed  Google Scholar 

  43. Abboud, S. & Haile, D. J. A novel mammalian iron-regulated protein involved in intracellular iron metabolism. J. Biol. Chem. 275, 19906–19912 ( 2000).

    Article  CAS  PubMed  Google Scholar 

  44. Harrison, P. M. & Arosio, P. The ferritins: molecular properties, iron storage function and cellular regulation. Biochim. Biophys. Acta 1275, 161–203 (1996).

    Article  PubMed  Google Scholar 

  45. Cossee, M. et al. Inactivation of the friedreich ataxia mouse gene leads to early embryonic lethality without iron accumulation. Hum. Mol. Genet. 9, 1219–1226 ( 2000).

    Article  CAS  PubMed  Google Scholar 

  46. Ferreira, C. et al. Early embryonic lethality of H ferritin gene deletion in mice . J. Biol. Chem. 275, 3021– 3024 (2000).

    Article  CAS  PubMed  Google Scholar 

  47. Feder, J. N. et al. A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nature Genet. 13, 399–408 (1996).The HFE gene (originally designated HLA-H ) is reported to be mutated in most patients with hereditary haemochromatosis.

    Article  CAS  PubMed  Google Scholar 

  48. Lebron, J. A. et al. Crystal structure of the hemochromatosis protein HFE and characterization of its interaction with transferrin receptor. Cell 93, 111–123 (1998).

    Article  CAS  PubMed  Google Scholar 

  49. Parkkila, S. et al. Association of the transferrin receptor in human placenta with HFE, the protein defective in hereditary haemochromatosis. Proc. Natl Acad. Sci. USA 94, 13198– 13202 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Bennett, M. J., Lebron, J. A. & Bjorkman, P. J. Crystal structure of the hereditary haemochromatosis protein HFE complexed with transferrin receptor. Nature 403, 46–53 (2000).

    Article  CAS  PubMed  Google Scholar 

  51. Bahram, S. et al. Experimental hemochromatosis due to MHC class I HFE deficiency: immune status and iron metabolism. Proc. Natl Acad. Sci. USA 96, 13312–13317 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Levy, J. E., Montross, L. K., Cohen, D. E., Fleming, M. D. & Andrews, N. C. The C282Y mutation causing hereditary hemochromatosis does not produce a null allele. Blood 94, 9–11 (1999). Mice lacking HFE have more severe iron loading than mice carrying the mutation found in human patients with haemochromatosis.

    CAS  PubMed  Google Scholar 

  53. Zhou, X. Y. et al. HFE gene knockout produces mouse model of hereditary hemochromatosis . Proc. Natl Acad. Sci. USA 95, 2492– 2497 (1998).Hfe knockout mice have iron overload, similar to human patients with haemochromatosis.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Levy, J. E., Montross, L. K. & Andrews, N. C. Genes that modify the hemochromatosis phenotype in mice. J. Clin. Invest. 105, 1209– 1216 (2000).Compound mutant mice, carrying mutations in Hfe and in genes involved in iron transport, show that iron overload in haemochromatosis occurs through the same transport pathway as normal iron uptake.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Cartwright, G. E., Gubler, C. J., Bush, J. A. & Wintrobe, M. M. Studies on copper metabolism. XVII. Further observations on the anemia of copper deficiency in swine. Blood 11, 143 (1956).

    CAS  PubMed  Google Scholar 

  56. Lee, G. R., Nacht, S., Lukens, J. N. & Cartwright, G. E. Iron metabolism in copper-deficient swine. J. Clin. Invest. 47, 2058–2069 (1968).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Osaki, S. & Johnson, D. A. Mobilization of liver iron by ferroxidase (ceruloplasmin). J. Biol. Chem. 244, 5757–5758 (1969).

    CAS  PubMed  Google Scholar 

  58. Osaki, S., Johnson, D. A. & Frieden, E. The mobilization of iron from the perfused mammalian liver by a serum copper enzyme, ferroxidase I. J. Biol. Chem. 246, 3018–3023 (1971).

    CAS  PubMed  Google Scholar 

  59. Harris, Z. L., Klomp, L. W. & Gitlin, J. D. Aceruloplasminemia: an inherited neurodegenerative disease with impairment of iron homeostasis. Am. J. Clin. Nutr. 67, S972–S977 ( 1998).

    Article  Google Scholar 

  60. Harris, Z. L. et al. Aceruloplasminemia: Molecular characterization of this disorder of iron metabolism. Proc. Natl Acad. Sci. USA 92, 2539–2543 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Morita, H. et al. Hereditary ceruloplasmin deficiency with hemosiderosis: a clinicopathological study of a Japanese family. Ann. Neurol. 37, 646–656 (1995).

    Article  CAS  PubMed  Google Scholar 

  62. Yoshida, K. et al. A mutation in the ceruloplasmin gene is associated with systemic hemosiderosis in humans. Nature Genet. 9, 267–272 (1995).

    Article  CAS  PubMed  Google Scholar 

  63. Harris, Z. L., Durley, A. P., Man, T. K. & Gitlin, J. D. Targeted gene disruption reveals an essential role for ceruloplasmin in cellular iron efflux. Proc. Natl Acad. Sci. USA 96, 10812–10817 (1999). This targeted disruption produced a mouse model for aceruloplasminaemia, and showed that ceruloplasmin is important for iron efflux from cells.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Levy, J. E., Jin, O., Fujiwara, Y., Kuo, F. & Andrews, N. C. Transferrin receptor is necessary for development of erythrocytes and the nervous system. Nature Genet. 21, 396–399 (1999). This targeted disruption of the transferrin receptor gene showed it to be essential for erythropoiesis but not for the early development of most other tissues.

    Article  CAS  PubMed  Google Scholar 

  65. Kawabata, H. et al. Molecular cloning of transferrin receptor 2. A new member of the transferrin receptor-like family. J. Biol. Chem. 274, 20826–20832 (1999).

    Article  CAS  PubMed  Google Scholar 

  66. Camaschella, C. et al. The gene TFR2 is mutated in a new type of haemochromatosis mapping to 7q22. Nature Genet. 25, 14– 15 (2000).This paper reported that a homologue of the transferrin receptor, TFR2, is mutated in some patients with non-HFE haemochromatosis.

    Article  CAS  PubMed  Google Scholar 

  67. Olynyk, J. K. et al. A population-based study of the clinical expression of the hemochromatosis gene. N. Engl. J. Med. 341, 718–724 (1999).

    Article  CAS  PubMed  Google Scholar 

  68. Mura, C., Raguenes, O. & Ferec, C. HFE mutations analysis in 711 hemochromatosis probands: evidence for S65C implication in mild form of hemochromatosis. Blood 93, 2502–2505 ( 1999).

    CAS  PubMed  Google Scholar 

  69. Gordeuk, V. et al. Iron overload in Africa. Interaction between a gene and dietary iron content. N. Engl. J. Med. 326, 95– 100 (1992).

    Article  CAS  PubMed  Google Scholar 

  70. Moyo, V. M. et al. Traditional beer consumption and the iron status of spouse pairs from a rural community in Zimbabwe. Blood 89, 2159–2166 (1997).

    CAS  PubMed  Google Scholar 

  71. Camaschella, C. et al. Juvenile and adult hemochromatosis are distinct genetic disorders . Eur. J. Hum. Genet. 5, 371– 375 (1997).

    CAS  PubMed  Google Scholar 

  72. Roetto, A. et al. Juvenile hemochromatosis locus maps to chromosome 1q. Am. J. Hum. Genet. 64, 1388–1393 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Pietrangelo, A. et al. Hereditary hemochromatosis in adults without pathogenic mutations in the hemochromatosis gene. N. Engl. J. Med. 341, 725–732 (1999).

    Article  CAS  PubMed  Google Scholar 

  74. Cox, T. C. et al. X-linked pyridoxine-responsive sideroblastic anemia due to a Thr388-to-Ser substitution in erythroid 5-aminolevulinate synthase. N. Engl. J. Med. 330, 675–679 (1994).

    Article  CAS  PubMed  Google Scholar 

  75. Beris, P. et al. Iron overload in patients with sideroblastic anaemia is not related to the presence of the haemochromatosis Cys282Tyr and His63Asp mutations. Br. J. Haematol. 104, 97–99 (1999).

    Article  CAS  PubMed  Google Scholar 

  76. Chiu, M. K. & Davey, A. M. Neonatal hemochromatosis. Clin. Pediatr. 36, 607–610 (1997).

    Article  CAS  Google Scholar 

  77. Edwards, C. Q. et al. Prevalence of hemochromatosis among 11,065 presumably healthy blood donors. N. Engl. J. Med. 318, 1355 –1362 (1988).

    Article  CAS  PubMed  Google Scholar 

  78. Simon, M., Bourel, M., Fauchet, R. & Genetet, B. Association of HLA-A3 and HLA-B14 antigens with idiopathic haemochromatosis. Gut 17, 332–334 ( 1976).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Pandolfo, M. Molecular pathogenesis of Friedreich ataxia. Arch. Neurol. 56, 1201–1208 (1999).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

I am grateful to all of the members of my laboratory for sharing their insights into iron metabolism. I appreciate help from Bernard Mathey-Prevot, Renee Ned, Carolyn Pettibone and Mark Fleming in providing criticism on an earlier version of the manuscript. Our studies are supported by the National Institutes of Health. I am an Associate Investigator of the Howard Hughes Medical Institute.

Author information

Authors and Affiliations

  1. Division of Hematology/Oncology Children's Hospital, Department of Pediatrics, Howard Hughes Medical Institute, Harvard Medical School, 300 Longwood Avenue, Boston, 02115, Massachusetts, USA

    Nancy C. Andrews

Authors
  1. Nancy C. Andrews
    View author publications

    You can also search for this author in PubMed Google Scholar

Supplementary information

Related links

Related links

DATABASE LINKS

Hereditary haemochromatosis

transferrin

ferritin

MK

SMF1

SMF2

DMT1

malvolio

(cdy)

hephaestin

ceruloplasmin

Weh

ferroportin1

mammalian ferroportin1

HFE

H-ferritin

frataxin

Friedreich ataxia

β2-microglobulin

ceruloplasmin gene

iron-loading disorder

TRFR

TFR2

FURTHER INFORMATION

Major histocompatibility complex

Nancy Andrews's homepage

ENCYCLOPEDIA OF LIFE SCIENCES

Iron deficiency

Iron overload and chelation therapy

Haem structure and function

Glossary

HAEM

Haem proteins contain an iron complex of porphyrin, usually protoporphyrin IX, and function as catalysts in many biological processes.

REDOX ACTIVITY

Oxidation and reduction activity, involving movement of electrons between different chemical entities.

CYTOCHROMES

Haemoproteins that take advantage of valence changes in haem iron to facilitate electron or hydrogen transport.

ERYTHROPOIESIS

The production of red blood cells. Erythropoiesis takes place in the bone marrow (humans and mice) and spleen (mice only).

PICA

Pica is the compulsive consumption of non-nutritive substances including paint chips, salt, ice and clay.

SIDEROBLASTIC ANAEMIA

Anaemia characterized by the presence of stainable iron granules in the cytoplasm of erythroid precursors (erythroblasts).

ACERULOPLASMINAEMIA

Absence of serum ceruloplasmin. An autosomal, recessive disorder, leading to neurodegenerative disease, liver iron overload and diabetes, caused by mutations in the ceruloplasmin gene.

TRANSFERRIN

An abundant plasma glycoprotein that binds iron with high affinity.

SYNCYTIOTROPHOBLAST

Part of the placenta; the syncytial outer layer of the trophoblast, through which the embryo receives nutrients from the mother.

ENTEROCYTES

Absorptive cells lining the intestine.

HEPATOCYTES

The parenchymal cells of the liver.

HOLOTRANSFERRIN

Transferrin loaded with iron.

APOTRANSFERRIN

Transferrin that does not contain bound iron.

MICROCYTIC

When red blood cells are smaller than normal, typically because of defects in haemoglobin production.

HYPOCHROMIC

When red blood cells are poorly haemoglobinized, typically because of defects in haemoglobin production.

ATRANSFERRINAEMIA

Absence of serum transferrin. An autosomal recessive disorder, associated with severe microcytic, hypochromic anaemia and tissue iron overload. Also called hypotransferrinaemia.

RETICULOCYTES

The youngest red blood cells normally found in the circulation, freshly released from the bone marrow (or other site of erythropoiesis).

NON-HAEM IRON

Iron from sources other than haem proteins.

SIDEROSIS

A general term for iron overload.

PHLEBOTOMY

Deliberate removal of venous blood from a patient.

HYDROPS

Swelling caused by the accumulation of fluid in tissues and the body cavity, which often occurs as a result of severe anaemia.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Andrews, N. Iron homeostasis: insights from genetics and animal models. Nat Rev Genet 1, 208–217 (2000). https://doi.org/10.1038/35042073

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/35042073

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing