Iron and Erythropoiesis

Lessons from Anemic Mice
  • Nancy C. Andrews
  • Mark D. Fleming


Iron deficiency and iron overload disorders are among the most common diseases afflicting modern man. Iron deficiency affects up to one billion individuals worldwide. Women and children are most commonly iron deficient, as a result of increased iron needs attributable to regular blood loss and rapid growth, respectively. Untreated iron deficiency in infants and toddlers can lead to irreversible cognitive deficits. Internationally, most iron deficiency can be traced to dietary insufficiency or subacute gastrointestinal hemorrhage associated with chronic parasitic infections. Rare patients have inherited defects in iron absorption or iron utilization. Iron deficiency is usually treatable with oral iron salts. While this treatment is inexpensive, it may be difficult to achieve compliance, because iron repletion takes several months to complete.


Iron Deficiency Iron Overload Iron Uptake Microcytic Anemia Intestinal Iron Absorption 
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  1. 1.
    Feder JN, Gnirke A, Thomas W, Tsuchihashi Z, Ruddy DA, Basava A, Dormishian F, Domingo R, Ellis MC, Fullan A, Hinton LM, Jones NL, Kimmel BE, Kronmal GS, Lauer R Lee VK, Loeb DB, Mapa FA, McClelland E, Meyer NC, Mintier GA, Moeller N, Moore T, Morikang E, Prass CE, Quin-tana L, Starnes SM, Schatzman RC, Brunke KJ, Drayna DT, Risch NJ, Bacon BR, Wolff RK: A novel MHC class Hike gene is mutated in patients with hereditary haemochromatosis. Nature Genetics 13: 399, 1996.PubMedCrossRefGoogle Scholar
  2. 2.
    Adams PC, Chakrabarti S: Genotypic/phenotypic correlations in genetic hemochromatosis: evolution of diagnostic criteria. Gastroenterology 114: 319, 1998.PubMedCrossRefGoogle Scholar
  3. 3.
    Gordeuk V, Mukiibi J, Hasstedt SJ, Samowitz W, Edwards CQ, West G, Ndambire S, Emmanual J, Nkanza N, Chapanduka Z, al. e: Iron overload in Africa. Interaction between a gene and dietary iron content. N Engl J Med 326: 126, 1992.CrossRefGoogle Scholar
  4. 4.
    Gordeuk V, McLaren C, Looker A, Hasselblad V, Brittenham G: Distribution of transferrin saturations in the African-American population. Blood 91: 2175, 1998.PubMedGoogle Scholar
  5. 5.
    Camaschella C, Roetto A, Cicilano M, Pasquero P, Bosio S, Gubetta L, Di Vito F, Girelli D, Totaro A, Carella M, Grifa A, Gasparini P: Juvenile and adult hemochromatosis are distinct genetic disorders. Eur J Hum Genet 5: 371, 1997.PubMedGoogle Scholar
  6. 6.
    Huggenvik JI, Craven CM, Idzerda RL, Bernstein S, Kaplan J, McKnight GS: A splicing defect in the mouse transferrin gene leads to congenital atransferrinemia. Blood 74: 482, 1989.PubMedGoogle Scholar
  7. 7.
    Nash DJ, Kent E, Dickie MM, Russell ES:The inheritance of “mick,” a new anemia in the house mouse [abstract]. American Zoologist 4: 404, 1964.Google Scholar
  8. 8.
    Russell ES, McFarland EC, Kent EL: Low viability, skin lesions, and reduced fertility associated with microcytic anemia in the mouse. Transpl Proc 2: 144, 1970.Google Scholar
  9. 9.
    Bannerman RM, Edwards JA, Kreimer-Birnbaum M, McFarland E, Russell ES: Hereditary microcytic anaemia in the mouse: studies in iron distribution and metabolism. British Journal of Haematology 23: 235, 1972.PubMedCrossRefGoogle Scholar
  10. 10.
    Edwards JA, Hoke JE: Defect of intestinal mucosal iron uptake in mice with hereditary microcytic anemia. Proc Soc Exp Biol Med 141: 81, 1972.PubMedGoogle Scholar
  11. 11.
    Harrison DE: Marrow Transplantation and Iron Therapy in Mouse Hereditary Microcytic Anemia. Blood 40: 893, 1972.PubMedGoogle Scholar
  12. 12.
    Edwards JA, Hoke JE: Red cell iron uptake in hereditary microcytic anemia. Blood 46: 381, 1975.PubMedGoogle Scholar
  13. 13.
    McFarland EC, Russell ES: Microcytic anemia (mk) has been located close to Ca on chromosome 15. Mouse News Letter 53: 35, 1975.Google Scholar
  14. 14.
    Russell ES, Nash DJ, Bernstein SE, Kent EL, McFarland EC, Matthews SM, Norwood MS: Characterization and genetic studies of microcytic anemia in house mouse. Blood 35: 838, 1970.PubMedGoogle Scholar
  15. 15.
    Handa S, Ferguson JM, Wallace ME, Bulfield G: Characterization and mapping of a viable anaemic mutant in the mouse: a new allele, mkvan, at the microcytic anaemia locus. Genetical Research 51: 41, 1987.CrossRefGoogle Scholar
  16. 16.
    Fleming MD, Trenor CC, Su MA, Foernzler D, Beier DR, Dietrich WF, Andrews NC: Microcytic anemia mice have a mutation in Nramp2, a candidate iron transporter. Nature Genetics 16: 383, 1997.PubMedGoogle Scholar
  17. 17.
    Grunheid S, Cellier M, Vidal S, Gros P: Identification and characterization of a second mouse Nramp gene. Genomics 25: 514, 1995.CrossRefGoogle Scholar
  18. 18.
    Vidal SM, Malo D, Vogan K, Skamene E, Gros P: Natural resistance to infection with intracellular parasites: isolation of a candidate for Bcg. Cell 73: 469, 1993.PubMedCrossRefGoogle Scholar
  19. 19.
    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, 1996.PubMedCrossRefGoogle Scholar
  20. 20.
    Thomson ABR, Olatunbosun D, Valberg LS: Interrelation of intestinal transport system for manganese and iron. J Lab Clin Med 78: 642, 1971.PubMedGoogle Scholar
  21. 21.
    Gunshin H, Mackenzie B, Berger UV, Gunshin Y, Romero MF, Boron WF. Nussberger S, Gollan JL, Hediger MA: Cloning and characterization of a mammalian proton-coupled metal-ion transporter. Nature 388: 482, 1997.PubMedCrossRefGoogle Scholar
  22. 22.
    Sladic-Simic D, Martinovich PN, Zivkovic N, Pavic D, Martinovic J, Kahn M, Ranney HM: A tha-lassemia-like disorder in Belgrade laboratory rats. Annals of the New York Academy of Sciences 165: 93, 1969.PubMedCrossRefGoogle Scholar
  23. 23.
    Edwards JA, Garrick LM, Hoke JE: Defective iron uptake and globin synthesis by erythroid cells in the anemia of the Belgrade laboratory rat. Blood 51: 347, 1978.PubMedGoogle Scholar
  24. 24.
    Garrick LM, Edwards JA, Hoke JE: The effect of hemin on globin synthesis and iron uptake by reticulocytes of the Belgrade rat. FEBS Letters 93: 109, 1978.PubMedCrossRefGoogle Scholar
  25. 25.
    Edwards JA, Sullivan AL, Hoke JE: Defective delivery of iron to the developing red cell of the Belgrade laboratory rat. Blood 55: 645, 1980.PubMedGoogle Scholar
  26. 26.
    Bowen BJ, Morgan EH: Anemia of the Belgrade rat: evidence for defective membrane transport of iron. Blood 70: 38, 1987.PubMedGoogle Scholar
  27. 27.
    Farcich EA, Morgan EH: Uptake of transferrin-bound and nontransferrin-bound iron by reticulocytes from the Belgrade laboratory rat: comparison with Wistar rat transferor, and reticulocytes. American Journal of Hematology 39: 9, 1992.PubMedCrossRefGoogle Scholar
  28. 28.
    Garrick MD, Gniecko K, Liu Y, Cohan DS, Garrick LM: Transferrin and the transferrin cycle in Belgrade rat reticulocytes. Journal of Biological Chemistry 20: 14867, 1993.Google Scholar
  29. 29.
    Fleming MD, Romano MA, Garrick LM, Garrick MD, Andrews NC: Anemia of the Belgrade rat is caused by a mutation in iron transporter protein Nramp2. Proc Natl Acad Sci USA 95: 1148, 1998.PubMedCrossRefGoogle Scholar
  30. 30.
    Su MA, Trenor CC, Fleming JC, Fleming MD, Andrews NC: The G185R mutation disrupts function of iron transporter Nramp2. Blood in press, 1998.Google Scholar
  31. 31.
    Garrick MD, Gniecko K, Liu L, Cohan DS, Garrick LM: Transferrin and the transferrin cycle in Belgrade rat reticulocytes. Journal of Biological Chemistry 268: 14867, 1993.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1999

Authors and Affiliations

  • Nancy C. Andrews
    • 1
    • 2
  • Mark D. Fleming
    • 1
    • 2
  1. 1.Howard Hughes Medical Institute and Division of Hematology/OncologyChildren’s HospitalUSA
  2. 2.Departments of Pathology and PediatricsHarvard Medical SchoolBostonUSA

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