Animal models of hereditary iron transport disorders

Advances in Experimental Medicine and Biology

Volumn 509, Issue , 2003, Pages 1-17

  Andrews, Nancy C ^a  

^a BOSTON CHILDREN S HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

IRON; IRON REGULATORY FACTOR; REGULATOR PROTEIN; TRANSFERRIN; TRANSFERRIN RECEPTOR;

ACERULOPLASMINEMIA; BIOACCUMULATION; DISEASE MODEL; DISORDERS OF METAL METABOLISM; FRIEDREICH ATAXIA; GENE DISRUPTION; GENE MUTATION; GENETIC DISORDER; GENETIC MANIPULATION; GENOME ANALYSIS; HEMOCHROMATOSIS; HUMAN; IRON ABSORPTION; IRON BALANCE; IRON DEFICIENCY; IRON INTAKE; IRON METABOLISM; IRON OVERLOAD; IRON STORAGE; IRON TRANSPORT; KNOCKOUT MOUSE; MICROCYTIC ANEMIA; MOUSE MUTANT; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; REVIEW; SIDEROBLASTIC ANEMIA; TISSUE DISTRIBUTION; TRANSFERRIN DEFICIENCY; ZEBRA FISH; ANIMAL; DISORDERS OF MITOCHONDRIAL FUNCTIONS; FEMALE; GENETICS; IRON METABOLISM DISORDER; MALE; METABOLISM; MOUSE; RAT; RAT STRAIN;

ANIMALIA; DANIO RERIO;

ANIMALS; DISEASE MODELS, ANIMAL; FEMALE; HEMOCHROMATOSIS; HUMANS; IRON; IRON METABOLISM DISORDERS; MALE; MICE; MICE, MUTANT STRAINS; MITOCHONDRIAL DISEASES; RATS; RATS, MUTANT STRAINS; TISSUE DISTRIBUTION; ZEBRAFISH;

EID: 0042810742     PISSN: 00652598     EISSN: None     Source Type: Book Series    
DOI: None     Document Type: Review

References (102)

1. Abboud, S., and Haile, D. J., 2000, A novel mammalian iron-regulated protein involved in intracellular iron metabolism. J Biol Chem 275, 19906-19912.
2. Allikmets, R., Raskind, W. H., Hutchinson, A., Schueck, N. D., Dean, M., and Koeller, D. M., 1999, Mutation of a putative mitochondrial iron transporter gene (ABC7) in X-linked sideroblastic anemia and ataxia (XLSA/A). Hum Mol Genet 8, 743-749.
3. Babcock, M., De Silva, D., Oaks, R., Davis-Kaplan, S., Jiralerspong, S., Montermini, L., Pandolfo, M., and Kaplan, J., 1997, Regulation of mitochondrial iron accumulation by Yfh1p, a putative homolog of frataxin. Science 276, 1709-1712.
4. Bahram, S., Gilfillan, S., Kuhn, L. C., Moret, R., Schulze, J. B., Lebeau, A., and Schumann, K., 1999, Experimental hemochromatosis due to MHC class I HFE deficiency: immune status and iron metabolism. Proc Natl Acad Sci USA 96, 13312-13317.
5. Bannerman, R. M., 1976, Genetic defects of iron transport Federation Proceedings 35, 2281.
6. Bannerman, R. M., and Cooper, R. G., 1966, Sex-linked anemia: a hypochromic anemia of mice. Science 151, 581-582.
7. Bannerman, R. M., Edwards, J. A., Kreimer-Birnbaum, M., McFarland, E., and Russell, E. S., 1972, Hereditary microcytic anaemia in the mouse; studies in iron distribution and metabolism. British Journal of Haematology 23, 235-245.
8. Bedard, Y. C., Pinkerton, P. H., and Simon, G. T., 1976, Uptake of circulating iron by the duodenum of normal mice and mice with altered iron stores, including sex-linked anemia. High resolution radioautographic study. Laboratory Investigation 34, 611-615.
9. Bekri, S., Kispal, G., Lange, H., Fitzsimons, E., Tolmie, J., Lill, R., and Bishop, D. F., 2000, Human ABC7 transporter: gene structure and mutation causing X-linked sideroblastic anemia with ataxia with disruption of cytosolic iron-sulfur protein maturation. Blood 96, 3256-3264.
10. Bennett, M., Pinkerton, P. H., Cudkowicz, G., and Bannerman, R. M., 1968, Hemopoietic progenitor cells in marrow and spleen of mice with hereditary iron deficiency anemia. Blood 32, 908-921.
11. Bernstein, S. E., 1987, Hereditary hypotransferrinemia with hemosiderosis, a murine disorder resembling human atransferrinemia. Journal of Laboratory and Clinical Medicine 110, 690-705.
12. Beutler, E., Felitti, V., Gelbart, T., and Ho, N., 2000a, The effect of HFE genotypes on measurements of iron overload in patients attending a health appraisal clinic. Ann Intern Med 133, 329-337.
13. Beutler, E., Gelbart, T., Lee, P., Trevino, R., Fernandez, M. A., and Fairbanks, V. F., 2000b, Molecular characterization of a case of atransferrinemia. Blood 96, 4071-4074.
14. Bloom, M. L., Simon-Stoos, K. L., and Mabon, M. E., 1998, The hemoglobin-deficit mutation is located on mouse chromosome 19. Mamm Genome 9, 666-667.
15. Bowen, B. J., and Morgan, E. H., 1987, Anemia of the Belgrade rat: evidence for defective membrane transport of iron. Blood 70, 38-44.
16. Brownlie, A., Donovan, A., Pratt, S., Paw, B., Oates, A., Brugnara, C., Witkowska, H., Sassa, S., and Zon, L., 1998, Positional cloning of the zebrafish sauternes gene: a model for congenital sideroblastic anaemia. Nat Genet 20, 244-250.
17. Bulaj, Z. J., Ajioka, R. S., Phillips, J. D., LaSalle, B. A., Jorde, L. B., Griffen, L. M., Edwards, C. Q., and Kushner, J. P., 2000, Disease-related conditions in relatives of patients with hemochromatosis. N Engl J Med 343, 1529-1535.
18. Camaschella, C., De Gobbi, M., and Roetto, A., 2001, Hereditary hemochromatosis: progress and perspectives. Rev Clin Exp Hematol 4, 302-321.
19. Camaschella, C., Roetto, A., Cali, A., De Gobbi, M., Garozzo, G., Carella, M., Majorano, N., Totaro, A., and Gasparini, P., 2000, The gene TFR2 is mutated in a new type of haemochromatosis mapping to 7q22. Nat Genet 25, 14-15.
20. Camaschella, C., Roetto, A., Cicilano, M., Pasquero, P., Bosio, S., Gubetta, L., Di Vito, F., Girelli, D., Totaro, A., Carella, M., Grifa, A., and Gasparini, P., 1997, Juvenile and adult hemochromatosis are distinct genetic disorders. Eur J Hum Genet 5, 371-375.
21. Campuzano, V., Montermini, L., Molto, M. D., Pianese, L., Cossee, M., Cavalcanti, F., Monros, E., Rodius, F., Duclos, F., Monticelli, A., and et al., 1996, Friedreich's ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science 271, 1423-1427.
22. Canonne-Hergaux, F., Fleming, M. D., Levy, J. E., Gauthier, S., Ralph, T., Picard, V., Andrews, N. C., and Gros, P., 2000, 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 96, 3964-3970.
23. Canonne-Hergaux, F., Gruenheid, S., Ponka, P., and Gros, P., 1999, Cellular and subcellular localization of the Nramp2 iron transporter in the intestinal brush border and regulation by dietary iron. Blood 93, 4406-4417.
24. Cazzola, M., Ascari, E., Barosi, G., Claudiani, G., Dacco, M., Kaltwasser, J. P., Panaiotopoulos, N., Schalk, K. P., and Werner, E. E., 1983, Juvenile idiopathic haemochromatosis: a life-threatening disorder presenting as hypogonadotropic hypogonadism. Hum Genet 65, 149-154.
25. Chua, A. C., and Morgan, E. H., 1997, Manganese metabolism is impaired in the Belgrade laboratory rat. J Comp Physiol 167, 361-369.
26. Cossee, M., Puccio, H., Gansmuller, A., Koutnikova, H., Dierich, A., LeMeur, M., Fischbeck, K., Dolle, P., and Koenig, M., 2000, Inactivation of the friedreich ataxia mouse gene leads to early embryonic lethality without iron accumulation. Hum Mol Genet 9, 1219-1226.
27. Cotter, P. D., May, A., Li, L., Al-Sabah, A. I., Fitzsimons, E. J., Cazzola, M., and Bishop, D. F., 1999, Four new mutations in the erythroid-specific 5-aminolevulinate synthase (ALAS2) gene causing X-linked sideroblastic anemia: increased pyridoxine responsiveness after removal of iron overload by phlebotomy and coinheritance of hereditary hemochromatosis. Blood 93, 1757-1769.
28. Cox, T. C., Bottomley, S. S., Wiley, J. S., Bawden, M. J., Matthews, C. S., and May, B. K., 1994, 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.
29. de Sousa, M., Reimao, R., Lacerda, R., Hugo, P., Kaufmann, S. H. E., and Porto, G., 1994, Iron overload in beta2-microglobulin deficient mice. Immunol Lett 39, 105-111.
30. Donovan, A., Brownlie, A., Pratt, S., Shepard, J., Paw, B., Dorschner, M. O., Fleming, M. D., Thisse, B., Andrews, N. C., and Zon, L. (1999). Positional cloning of two zebrafish mutant genes involved in hypochromic anemia: the iron transporter DMT1 (Nramp2) and a novel integral membrane protein. Paper presented at: BioIron 1999 (Sorrento, Italy).
31. Donovan, A., Brownlie, A., Zhou, Y., Shepard, J., Pratt, S. J., Moynihan, J., Paw, B. H., Drejer, A., Barut, B., Zapata, A., Law, T. C., Brugnara, C., Lux, S. E., Pinkus, G. S., Pinkus, J. L., Kingsley, P. D., Palis, J., Fleming, M. D., Andrews, N. C., and Zon, L. I., 2000, Positional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter. Nature 403, 776-781.
32. Edwards, J., Huebers, H., Kunzler, C., and Finch, C., 1986, Iron metabolism in the Belgrade rat. Blood 67, 623-628.
33. Edwards, J. A., and Bannerman, R. M., 1970, Hereditary defect of intestinal iron transport in mice with sex-linked anemia. J Clin Invest 49, 1869-1871.
34. Edwards, J. A., and Hoke, J. E., 1972, Defect of intestinal mucosal iron uptake in mice with hereditary microcytic anemia. Proc Soc Exp Biol Med 141, 81-84.
35. Edwards, J. A., and Hoke, J. E., 1975, Red cell iron uptake in hereditary microcytic anemia. Blood 46, 381-388.
36. Edwards, J. A., Sullivan, A. L., and Hoke, J. E., 1980, Defective delivery of iron to the developing red cell of the Belgrade laboratory rat. Blood 55, 645-648.
37. Eisenstein, R. S., 2000, Iron regulatory proteins and the molecular control of mammalian iron metabolism. Annu Rev Nutr 20, 627-662.
38. Falconer, D. S., and Isaacson, J. H., 1962, The genetics of sex-linked anaemia in the mouse. Genet Res 3, 248-250.
39. Farcich, E. A., and Morgan, E. H., 1992a, Diminished iron acquisition by cells and tissues of Belgrade laboratory rats. Am J Physiol 262, R220-224.
40. Farcich, E. A., and Morgan, E. H., 1992b, Uptake of transferrin-bound and nontransferrin-bound iron by reticulocytes from the Belgrade laboratory rat: comparison with Wistar rat transferrin and reticulocytes. American Journal of Hematology 39, 9-14.
41. Feder, J. N., Gnirke, A., Thomas, W., Tsuchihashi, Z., Ruddy, D. A., Basava, A., Dormishian, F., Domingo, R., Ellis, M. C., Fullan, A., Hinton, L. M., Jones, N. L., Kimmel, B. E., Kronmal, G. S., Lauer, P., Lee, V. K., Loeb, D. B., Mapa, F. A., McClelland, E., Meyer, N. C., Mintier, G. A., Moeller, N., Moore, T., Morikang, E., Prass, C. E., Quintana, L., Starnes, S. M., Schatzman, R. C., Brunke, K. J., Drayna, D. T., Risch, N. J., Bacon, B. R., and Wolff, R. K., 1996, A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nature Genetics 13, 399-408.
42. Ferreira, C., Bucchini, D., Martin, M. E., Levi, S., Arosio, P., Grandchamp, B., and Beaumont, C., 2000, Early embryonic lethality of H ferritin gene deletion in mice. J Biol Chem 275, 3021-3024.
43. Flanagan, P. R., Haist, J., MacKenzie, I., and Valberg, L. S., 1984, Intestinal absorption of zinc: competitive interactions with iron, cobalt and copper in mice with sex-linked anemia (sla). Canadian Journal of Physiology and Pharmacology 62, 1124-1128.
44. Fleming, M. D., Campagna, D. R., Haslett, J. N., Trenor, C. C., 3rd, and Andrews, N. C., 2001a, A mutation in a mitochondrial transmembrane protein is responsible for the pleiotropic hematological and skeletal phenotype of flexed-tail (f/f) mice. Genes Dev 15, 652-657.
45. Fleming, M. D., Romano, M. A., Su, M. A., Garrick, L. M., Garrick, M. D., and Andrews, N. C., 1998, 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.
46. Fleming, M. D., Trenor, C. C. I., Su, M. A., Foernzler, D., Beier, D. R., Dietrich, W. F., and Andrews, N. C., 1997, Microcytic anemia mice have a mutation in Nramp2, a candidate iron transporter gene. Nature Genetics 16, 383-386.
47. Fleming, R. E., Holden, C. C., Tomatsu, S., Waheed, A., Brunt, E. M., Britton, R. S., Bacon, B. R., Roopenian, D. C., and Sly, W. S., 2001b, Mouse strain differences determine severity of iron accumulation in Hfe knockout model of hereditary hemochromatosis. Proc Natl Acad Sci USA 98, 2707-2711.
48. Garrick, L. M., Edwards, J. A., Hoke, J. E., and Bannerman, R. M., 1987, Diminished acquisition of iron by reticulocytes from mice with hemoglobin deficit. Experimental Hematology 15, 671-675.
49. Garrick, M. D., Gniecko, K., Liu, L., Cohan, D. S., and Garrick, L. M., 1993, Transferrin and the transferrin cycle in Belgrade rat reticulocytes. Journal of Biological Chemistry 268, 14867.
50. Goya, N., Miyazaki, S., Kodate, S., and Ushio, B., 1972, A family of congenital atransferrinemia. Blood 40, 239-245.
51. Grewal, M. D., 1962, A sex-linked anaemia in the mouse. Genet Res 3, 238-247.
52. Gruenheid, S., Canonne-Hergaux, F., Gauthier, S., Hackam, D. J., Grinstein, S., and Gros, P., 1999, The iron transport protein NRAMP2 is an integral membrane glycoprotein that colocalizes with transferrin in recycling endosomes. J Exp Med 189, 831-841.
53. Gruneberg, H., 1942, The anaemia of flexed-tail mice (Mus musculus L.). 11. Siderocytes. J Genet 44, 246-271.
54. Gunshin, H., Mackenzie, B., Berger, U. V., Gunshin, Y., Romero, M. F., Boron, W. F., Nussberger, S., Gollan, J. L., and Hediger, M. A., 1997, Cloning and characterization of a mammalian proton-coupled metal-ion transporter. Nature 388, 482-488.
55. Haffter, P., Granato, M., Brand, M., Mullins, M. C., Hammerschmidt, M., Kane, D. A., Odenthal, J., van Eeden, F. J., Jiang, Y. J., Heisenberg, C. P., Kelsh, R. N., Furutani-Seiki, M., Vogelsang, E., Beuchle, D., Schach, U., Fabian, C., and Nusslein-Volhard, C., 1996, The identification of genes with unique and essential functions in the development of the zebrafish, Danio rerio. Development 123, 1-36.
56. Hamill, R. L., Woods, J. C., and Cook, B. A., 1991, Congenital atransferrinemia: a case report and review of the literature. American Journal of Clinical Pathology 96, 215-218.
57. Harris, Z. L., Durley, A. P., Man, T. K., and Gitlin, J. D., 1999, Targeted gene disruption reveals an essential role for ceruloplasmin in cellular iron efflux. Proc Natl Acad Sci USA 96, 10812-10817.
58. Harris, Z. L., Klomp, L. W., and Gitlin, J. D., 1998, Aceruloplasminemia: an inherited neurodegenerative disease with impairment of iron homeostasis. Am J Clin Nutr 61, 972S-977S.
59. Harris, Z. L., Takahashi, Y., Miyajima, H., Serizawa, M., MacGillivray, R. T. A., and Gitlin, J. D., 1995, Aceruloplasminemia: Molecular characterization of this disorder of iron metabolism. Proceedings of the National Academy of Sciences (USA) 92, 2539-2543.
60. Harrison, D. E., 1972, Marrow Transplantation and Iron Therapy in Mouse Hereditary Microcytic Anemia. Blood 40, 893-901.
61. Heilmeyer, L., 1966, Atransferrinemias [German]. Acta Haematologica 36, 40-49.
62. Holmberg, C. G., and Laurell, C. B., 1948, Acta Chem Scand 2, 550-556.
63. Huggenvik, J. I., Craven, C. M., Idzerda, R. L., Bernstein, S., Kaplan, J., and McKnight, G. S., 1989, A splicing defect in the mouse transferrin gene leads to congenital atransferrinemia. Blood 74, 482-486.
64. Kingston, P. J., Bannerman, C. E., and Bannerman, R. M., 1978, Iron deficiency anaemia in newborn sla mice: a genetic defect of placental iron transport. Br J Haematol 40, 265-276.
65. Koller, B. H., Marrack, P., Kappler, J. W., and Smithies, O., 1990, Normal development of mice deficient in beta 2M, MHC class I proteins, and CD8+ T cells. Science 248, 1227-1230.
66. LaVaute, T., Smith, S., Cooperman, S., Iwai, K., Land, W., Meyron-Holtz, E., Drake, S. K., Miller, G., Abu-Asab, M., Tsokos, M., Switzer, R., Grinberg, A., Love, P., Tresser, N., and Rouault, T. A., 2001, Targeted deletion of the gene encoding iron regulatory protein-2 causes misregulation of iron metabolism and neurodegenerative disease in mice. Nat Genet 27, 209-214.
67. Lebron, J. A., Bennett, M. J., Vaughn, D. E., Chirino, A. J., Snow, P. M., Mintier, G. A., Feder, J. N., and Bjorkman, P. J., 1998, Crystal structure of the hemochromatosis protein HFE and characterization of its interaction with transferrin receptor. Cell 93, 111-123.
68. Levy, J. E., Jin, O., Fujiwara, Y., Kuo, F., and Andrews, N. C., 1999a, Transferrin receptor is necessary for development of erythrocytes and the nervous system. Nature Genet 21, 396-399.
69. Levy, J. E., Montross, L. K., and Andrews, N. C., 2000, Genes that modify the hemochromatosis phenotype in mice. J Clin Invest 105, 1209-1216.
70. Levy, J. E., Montross, L. K., Cohen, D. E., Fleming, M. D., and Andrews, N. C., 1999b, The C282Y mutation causing hereditary hemochromatosis does not produce a null allele. Blood 94, 9-11.
71. Manis, J., 1971, Intestinal iron-transport defect in the mouse with sex-linked anemia. American Journal of Physiology 220, 135-139.
72. McKie, A. T., Marciani, P., Rolfs, A., Brennan, K., Wehr, K., Barrow, D., Miret, S., Bomford, A., Peters, T. J., Farzaneh, F., Hediger, M. A., Hentze, M. W., and Simpson, R. J., 2000, A novel duodenal iron-regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation. Mol Cells 5, 299-309.
73. Miyajima, H., Takahashi, Y., Kamata, T., Shimizu, H., Sakai, N., and Gitlin, J. D., 1997, Use of desferrioxamine in the treatment of aceruloplasminemia. Ann Neurol 41, 404-407.
74. Miyajima, H., Takahashi, Y., Shimizu, H., Sakai, N., Kamata, T., and Kaneko, E., 1996, Late onset diabetes mellitus in patients with hereditary aceruloplasminemia. Intern Med 35, 641-645.
75. Nakajima, O., Takahashi, S., Harigae, H., Furuyama, K., Hayashi, N., Sassa, S., and Yamamoto, M., 1999, Heme deficiency in erythroid lineage causes differentiation arrest and cytoplasmic iron overload. Embo J 18, 6282-6289.
76. Nash, D. J., Kent, E., Dickie, M. M., and Russell, E. S., 1964, The inheritance of "mick," a new anemia in the house mouse [abstract], American Zoologist 4, 404-405.
77. Oates, P. S., and Morgan, E. H., 1996, Defective iron uptake by the duodenum of Belgrade rats fed diets of different iron contents. Am J Physiol 270, G826-832.
78. Okamoto, N., Wada, S., Oga, T., Kawabata, Y., Baba, Y., Habu, D., Takeda, Z., and Wada, Y., 1996, Hereditary ceruloplasmin deficiency with hemosiderosis. Hum Genet 97, 755-758.
79. Phillips, J. D., Jackson, L. K., Bunting, M., Franklin, M. R., Thomas, K. R., Levy, J. E., Andrews, N. C., and Kushner, J. P., 2001, A mouse model of familial porphyria cutanea tarda. Proc Natl Acad Sci USA 98, 259-264.
80. Pietrangelo, A., Montosi, G., Totaro, A., Garuti, C., Conte, D., Cassanelli, S., Fraquelli, M., Sardini, C., Vasta, F., and Gasparini, P., 1999, Hereditary Hemochromatosis in Adults without Pathogenic Mutations in the Hemochromatosis Gene. N Engl J Med 341, 725-732.
81. Pinkerton, P. H., 1968, Histological evidence of disordered iron transport in the x-linked hypochromic anaemia of mice. J Pathol Bacterial 95, 155-165.
82. Pinkerton, P. H., Bannerman, R. M., Doeblin, T. D., Benisch, B. M., and Edwards, J. A., 1970, Iron metabolism and absorption studies in the X-linked anaemia of mice. Br J Haematol 18, 211-228.
83. Puccio, H., Simon, D., Cossee, M., Criqui-Filipe, P., Tiziano, F., Melki, J., Hindelang, C., Matyas, R., Rustin, P., and Koenig, M., 2001, Mouse models for Friedreich ataxia exhibit cardiomyopathy, sensory nerve defect and Fe-S enzyme deficiency followed by intramitochondrial iron deposits. Nat Genet 27, 181-186.
84. Rothenberg, B. E., and Voland, J. R., 1996, Beta 2 knockout mice deveop parenchymal iron overload: a putative role for class I genes of the major histocompatibility complex in iron metabolism. Proceedings of the National Academy of Sciences (USA) 93, 1529-1534.
85. Russell, E. S., 1984, Developmental studies of mouse hereditary anemias. Am J Med Genet 18, 621-641.
86. Russell, E. S., McFarland, E. C., and Kent, E. L., 1970, Low viability, skin lesions, and reduced fertility associated with microcytic anemia in the mouse. Transpl Proc 2, 144-151.
87. Santos, M., Schilham, M. W., Rademakers, L. H. P. M., Marx, J. J. M., deSousa, M., and Clevers, M., 1996, Defective iron homeostasis in beta2-microglobulin knockout mice recapitulates hereditary hemochromatosis in man. J Exp Med 184, 1975-1985.
88. Scheufler, V. H., 1969, Eine weitere Mutante der Hausmaus mit Anamie (hbd). Z Versuchstierk 11, 348-353.
89. Sham, R. L., Raubertas, R. F., Braggins, C., Cappuccio, J., Gallagher, M., and Phatak, P. D., 2000, Asymptomatic hemochromatosis subjects: genotypic and phenotypic profiles. Blood 96, 3707-3711.
90. Simon, M., Bourel, M., Fauchet, R., and Genetet, B., 1976, Association of HLA-A3 and HLA-B14 antigens with idiopathic haemochromatosis. Gut 17, 332-334.
91. Simpson, R. J., Cooper, C. E., Raja, K. B., Halliwell, B., Evans, P. J., Aruoma, O. I., Singh, S., and Konijn, A. M., 1992, Non-transferrin-bound iron species in the serum of hypotransferrinaemic mice. Biochim Biophys Acta 1156, 19-26.
92. Simpson, R. J., Konijn, A. M., Lombard, M., Raja, K. B., Salisbury, J. R., and Peters, T. J., 1993, Tissue iron loading and histopathological changes in hypotransferrinaemic mice. J Pathol 171, 237-244.
93. Sinclair, P. R., Gorman, N., Walton, H. S., Bement, W. J., Sinclair, J. F., Gerhard, G. S., Szakacs, J. G., Andrews, N. C., and Levy, J. E., 2001, Uroporphyria in Hfe mutant mice given 5-aminolevulinate: A new model of Fe-mediated porphyria cutanea tarda. Hepatology 33, 406-412.
94. Sladic-Simic, D., Martinovich, P. N., Zivkovic, N., Pavic, D., Martinovic, J., Kahn, M., and Ranney, H. M., 1969, A thalassemia-like disorder in Belgrade laboratory rats. Annals of the New York Academy of Sciences 165, 93-99.
95. Sproule, T. J., Jazwinska, E. C., Britton, R. S., Bacon, B. R., Fleming, R. E., Sly, W. S., and Roopenian, D. C., 2001, Naturally variant autosomal and sex-linked loci determine the severity of iron overload in beta 2-microglobulin-deficient mice. Proc Natl Acad Sci USA 98, 5170-5174.
96. Su, M. A., Trenor, C. C., Fleming, J. C., Fleming, M. D., and Andrews, N. C., 1998, The G185R mutation disrupts function of iron transporter Nramp2. Blood 92, 2157-2163.
97. Theil, E. C., Takagi, H., Small, G. W., He, L., Tipton, A. R., and Danger, D., 1999, The ferritin iron entry and exit problem. Inorganica Clinica Acta 297, 242-251.
98. Trenor, C. C. I., Campagna, D. R., Sellers, V. M., Andrews, N. C., and Fleming, M. D., 2000, The molecular defect in hypotransferrinemic mice. Blood 96, 1113-1118.
99. Vulpe, C. D., Kuo, Y. M., Murphy, T. L., Cowley, L., Askwith, C., Libina, N., Gitschier, J., and Anderson, G. J., 1999, Hephaestin, a ceruloplasmin homologue implicated in intestinal iron transport, is defective in the sla mouse. Nature Genet 21, 195-199.
100. Yoshida, K., Furihata, K., Takeda, S., Nakamura, A., Yamamoto, K., Morita, H., Hiyamuta, S., Ikeda, S., Shimizu, N., and Yanagisawa, N., 1995, A mutation in the ceruloplasmin gene is associated with systemic hemosiderosis in humans. Nat Genet 9, 267-272.
101. Zhou, X. Y., Tomatsu, S., Fleming, R. E., Parkkila, S., Waheed, A., Jiang, J., Fei, Y., Brunt, E. M., Ruddy, D. A., Prass, C. E., Schatzman, R. C., O'Neill, R., Britton, R. S., Bacon, B. R., and Sly, W. S., 1998, HFE gene knockout produces mouse model of hereditary hemochromatosis. Proc Natl Acad Sci USA 95, 2492-2497.
102. Zijlstra, M., Bix, M., Simister, N. E., Loring, J. M., Raulet, D. H., and Jaenisch, R., 1990, Beta 2-microglobulin deficient mice lack CD4-8+ cytolytic T cells. Nature 344, 742-746.