Iron homeostasis: insights from genetics and animal models
10.1038/35042073
Crossref journal-article
Springer Science and Business Media LLC
Nature Reviews Genetics (297)
Bibliography

Andrews, N. C. (2000). Iron homeostasis: insights from genetics and animal models. Nature Reviews Genetics, 1(3), 208–217.

Authors 1
  1. Nancy C. Andrews (first)
References 79 Referenced 335
  1. Finch, C. Regulators of iron balance in humans. Blood 84, 1697–1702 (1994). (10.1182/blood.V84.6.1697.1697) / Blood by C Finch (1994)
  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). (10.1097/00043426-199909000-00004) / J. Pediatr. Hematol. Oncol. by NC Andrews (1999)
  3. Buchanan, G. R. & Sheehan, R. G. Malabsorption and defective utilization of iron in three siblings. J. Pediatr. 98, 723–728 ( 1981). (10.1016/S0022-3476(81)80831-1) / J. Pediatr. by GR Buchanan (1981)
  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). (10.1002/(SICI)1096-8652(199604)51:4<269::AID-AJH4>3.0.CO;2-U) / Am. J. Hematol. by KR Hartman (1996)
  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). (10.1097/00043426-199909000-00014) / J. Pediatr. Hematol. Oncol. by HA Pearson (1999)
  6. Schade, A. L. & Caroline, L. An iron-binding component in human blood plasma. Science 104, 340– 341 (1946). (10.1126/science.104.2702.340) / Science by AL Schade (1946)
  7. Bannerman, R. M. Genetic defects of iron transport. Fed. Proc. 35, 2281 (1976). / Fed. Proc. by RM Bannerman (1976)
  8. Bernstein, S. E. Hereditary hypotransferrinemia with hemosiderosis, a murine disorder resembling human atransferrinemia. J. Lab. Clin. Med. 110, 690–705 (1987). / J. Lab. Clin. Med. by SE Bernstein (1987)
  9. Huggenvik, J. I. et al. A splicing defect in the mouse transferrin gene leads to congenital atransferrinemia. Blood 74, 482– 486 (1989). (10.1182/blood.V74.1.482.482) / Blood by JI Huggenvik (1989)
  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). (10.1182/blood.V96.3.1113) / Blood by CC Trenor (2000)
  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). (10.1111/j.1749-6632.1988.tb55498.x) / Ann. NY Acad. Sci. by J Kaplan (1988)
  12. Simpson, R. J. et al. Tissue iron loading and histopathological changes in hypotransferrinaemic mice. J. Pathol. 171, 237– 244 (1993). (10.1002/path.1711710313) / J. Pathol. by RJ Simpson (1993)
  13. Heilmeyer, L. et al. Congenital transferrin deficiency in a seven-year old girl . German Med. Mon. 86, 1745– 1751 (1961). / German Med. Mon. by L Heilmeyer (1961)
  14. Goya, N., Miyazaki, S., Kodate, S. & Ushio, B. A family of congenital atransferrinemia. Blood 40, 239– 245 (1972). (10.1182/blood.V40.2.239.239) / Blood by N Goya (1972)
  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). (10.1093/ajcp/96.2.215) / Am. J. Clin. Pathol. by RL Hamill (1991)
  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). / Transpl. Proc. by ES Russell (1970)
  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). (10.3181/00379727-141-36720) / Proc. Soc. Exp. Biol. Med. by JA Edwards (1972)
  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). (10.1042/bj3090745) / Biochem. J. by HD Riedel (1995)
  19. Edwards, J. A. & Hoke, J. E. Red cell iron uptake in hereditary microcytic anemia. Blood 46, 381–388 (1975). (10.1182/blood.V46.3.381.381) / Blood by JA Edwards (1975)
  20. Harrison, D. E. Marrow transplantation and iron therapy in mouse hereditary microcytic anemia . Blood 40, 893–901 (1972). (10.1182/blood.V40.6.893.893) / Blood by DE Harrison (1972)
  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. (10.1038/ng0897-383) / Nature Genet. by MD Fleming (1997)
  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). (10.1073/pnas.93.10.5105) / Proc. Natl Acad. Sci. USA by F Supek (1996)
  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. (10.1038/41343) / Nature by H Gunshin (1997)
  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). (10.1182/blood.V92.6.2157) / Blood by MA Su (1998)
  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). / Am. J. Physiol. by PS Oates (1996)
  27. Sladic-Simic, D. et al. A thalassemia-like disorder in Belgrade laboratory rats. Ann. NY Acad. Sci. 165, 93–99 (1969). (10.1111/j.1749-6632.1969.tb27779.x) / Ann. NY Acad. Sci. by D Sladic-Simic (1969)
  28. Bowen, B. J. & Morgan, E. H. Anemia of the Belgrade rat: evidence for defective membrane transport of iron. Blood 70, 38–44 (1987). (10.1182/blood.V70.1.38.38) / Blood by BJ Bowen (1987)
  29. Edwards, J., Huebers, H., Kunzler, C. & Finch, C. Iron metabolism in the Belgrade rat. Blood 67, 623– 628 (1986). (10.1182/blood.V67.3.623.623) / Blood by J Edwards (1986)
  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. (10.1073/pnas.95.3.1148) / Proc. Natl Acad. Sci. USA by MD Fleming (1998)
  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). (10.1182/blood.V93.12.4406) / Blood by F Canonne-Hergaux (1999)
  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). (10.1084/jem.189.5.831) / J. Exp. Med. by S Gruenheid (1999)
  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). / Am. J. Physiol. by EA Farcich (1992)
  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). (10.1002/j.1460-2075.1995.tb07303.x) / EMBO J. by V Rodrigues (1995)
  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). (10.1242/jeb.201.1.115) / J. Exp. Biol. by S Orgad (1998)
  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). (10.1242/dev.123.1.1) / Development by P Haffter (1996)
  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). (10.1111/j.1365-2141.1978.tb03663.x) / Br. J. Haematol. by PJ Kingston (1978)
  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). (10.1172/JCI106405) / J. Clin. Invest. by JA Edwards (1970)
  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). (10.1111/j.1365-2141.1970.tb01435.x) / Br. J. Haematol. by PH Pinkerton (1970)
  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. (10.1038/5979) / Nature Genet. by C Vulpe (1999)
  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. (10.1038/35001596) / Nature by A Donovan (2000)
  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. (10.1016/S1097-2765(00)80425-6) / Mol. Cell by AT McKie (2000)
  43. Abboud, S. & Haile, D. J. A novel mammalian iron-regulated protein involved in intracellular iron metabolism. J. Biol. Chem. 275, 19906–19912 ( 2000). (10.1074/jbc.M000713200) / J. Biol. Chem. by S Abboud (2000)
  44. Harrison, P. M. & Arosio, P. The ferritins: molecular properties, iron storage function and cellular regulation. Biochim. Biophys. Acta 1275, 161–203 (1996). (10.1016/0005-2728(96)00022-9) / Biochim. Biophys. Acta by PM Harrison (1996)
  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). (10.1093/hmg/9.8.1219) / Hum. Mol. Genet. by M Cossee (2000)
  46. Ferreira, C. et al. Early embryonic lethality of H ferritin gene deletion in mice . J. Biol. Chem. 275, 3021– 3024 (2000). (10.1074/jbc.275.5.3021) / J. Biol. Chem. by C Ferreira (2000)
  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. (10.1038/ng0896-399) / Nature Genet. by JN Feder (1996)
  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). (10.1016/S0092-8674(00)81151-4) / Cell by JA Lebron (1998)
  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). (10.1073/pnas.94.24.13198) / Proc. Natl Acad. Sci. USA by S Parkkila (1997)
  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). (10.1038/47417) / Nature by MJ Bennett (2000)
  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). (10.1073/pnas.96.23.13312) / Proc. Natl Acad. Sci. USA by S Bahram (1999)
  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. (10.1182/blood.V94.1.9.413a43_9_11) / Blood by JE Levy (1999)
  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. (10.1073/pnas.95.5.2492) / Proc. Natl Acad. Sci. USA by XY Zhou (1998)
  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. (10.1172/JCI9635) / J. Clin. Invest. by JE Levy (2000)
  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). (10.1182/blood.V11.2.143.143) / Blood by GE Cartwright (1956)
  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). (10.1172/JCI105891) / J. Clin. Invest. by GR Lee (1968)
  57. Osaki, S. & Johnson, D. A. Mobilization of liver iron by ferroxidase (ceruloplasmin). J. Biol. Chem. 244, 5757–5758 (1969). (10.1016/S0021-9258(18)63623-3) / J. Biol. Chem. by S Osaki (1969)
  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). (10.1016/S0021-9258(18)62284-7) / J. Biol. Chem. by S Osaki (1971)
  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). (10.1093/ajcn/67.5.972S) / Am. J. Clin. Nutr. by ZL Harris (1998)
  60. Harris, Z. L. et al. Aceruloplasminemia: Molecular characterization of this disorder of iron metabolism. Proc. Natl Acad. Sci. USA 92, 2539–2543 (1995). (10.1073/pnas.92.7.2539) / Proc. Natl Acad. Sci. USA by ZL Harris (1995)
  61. Morita, H. et al. Hereditary ceruloplasmin deficiency with hemosiderosis: a clinicopathological study of a Japanese family. Ann. Neurol. 37, 646–656 (1995). (10.1002/ana.410370515) / Ann. Neurol. by H Morita (1995)
  62. Yoshida, K. et al. A mutation in the ceruloplasmin gene is associated with systemic hemosiderosis in humans. Nature Genet. 9, 267–272 (1995). (10.1038/ng0395-267) / Nature Genet. by K Yoshida (1995)
  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. (10.1073/pnas.96.19.10812) / Proc. Natl Acad. Sci. USA by ZL Harris (1999)
  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. (10.1038/7727) / Nature Genet. by JE Levy (1999)
  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). (10.1074/jbc.274.30.20826) / J. Biol. Chem. by H Kawabata (1999)
  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. (10.1038/75534) / Nature Genet. by C Camaschella (2000)
  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). (10.1056/NEJM199909023411002) / N. Engl. J. Med. by JK Olynyk (1999)
  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). (10.1182/blood.V93.8.2502) / Blood by C Mura (1999)
  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). (10.1056/NEJM199201093260204) / N. Engl. J. Med. by V Gordeuk (1992)
  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). (10.1182/blood.V89.6.2159) / Blood by VM Moyo (1997)
  71. Camaschella, C. et al. Juvenile and adult hemochromatosis are distinct genetic disorders . Eur. J. Hum. Genet. 5, 371– 375 (1997). (10.1159/000484794) / Eur. J. Hum. Genet. by C Camaschella (1997)
  72. Roetto, A. et al. Juvenile hemochromatosis locus maps to chromosome 1q. Am. J. Hum. Genet. 64, 1388–1393 (1999). (10.1086/302379) / Am. J. Hum. Genet. by A Roetto (1999)
  73. Pietrangelo, A. et al. Hereditary hemochromatosis in adults without pathogenic mutations in the hemochromatosis gene. N. Engl. J. Med. 341, 725–732 (1999). (10.1056/NEJM199909023411003) / N. Engl. J. Med. by A Pietrangelo (1999)
  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). (10.1056/NEJM199403103301004) / N. Engl. J. Med. by TC Cox (1994)
  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). (10.1046/j.1365-2141.1999.01142.x) / Br. J. Haematol. by P Beris (1999)
  76. Chiu, M. K. & Davey, A. M. Neonatal hemochromatosis. Clin. Pediatr. 36, 607–610 (1997). (10.1177/000992289703601012) / Clin. Pediatr. by MK Chiu (1997)
  77. Edwards, C. Q. et al. Prevalence of hemochromatosis among 11,065 presumably healthy blood donors. N. Engl. J. Med. 318, 1355 –1362 (1988). (10.1056/NEJM198805263182103) / N. Engl. J. Med. by CQ Edwards (1988)
  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). (10.1136/gut.17.5.332) / Gut by M Simon (1976)
  79. Pandolfo, M. Molecular pathogenesis of Friedreich ataxia. Arch. Neurol. 56, 1201–1208 (1999). (10.1001/archneur.56.10.1201) / Arch. Neurol. by M Pandolfo (1999)
Dates
Type When
Created 23 years ago (July 26, 2002, 4:48 a.m.)
Deposited 2 years, 3 months ago (May 16, 2023, 10:14 p.m.)
Indexed 2 weeks, 2 days ago (Aug. 7, 2025, 4:51 a.m.)
Issued 24 years, 8 months ago (Dec. 1, 2000)
Published 24 years, 8 months ago (Dec. 1, 2000)
Published Print 24 years, 8 months ago (Dec. 1, 2000)
Funders 0

None

@article{Andrews_2000, title={Iron homeostasis: insights from genetics and animal models}, volume={1}, ISSN={1471-0064}, url={http://dx.doi.org/10.1038/35042073}, DOI={10.1038/35042073}, number={3}, journal={Nature Reviews Genetics}, publisher={Springer Science and Business Media LLC}, author={Andrews, Nancy C.}, year={2000}, month=dec, pages={208–217} }