Table 1.
Mouse Models and Corresponding Human Disorders of Iron Metabolism
Gene | Mouse model | Iron phenotype | Human disease parallel | Reference |
---|---|---|---|---|
Abcb7 | Abcb7−/− | Siderocytosis | X-linked sideroblastic anemia | (153) |
Abcb7E433K | ||||
Aco1 | Irp1−/− | NA | Cardiac problems | (163) |
Alas2 | Alas2−/− | Increased iron in primitive erythroid cells | X-linked sideroblastic anemia | (153) |
Beta-2 microglobulin | B2m−/− | Parenchymal iron deposition; decreased hepcidin | ND | (382) |
Bmp6 | Bmp6−/− | Increased body iron; decreased hepcidin | ND | (16, 304) |
Ceruloplasmin | Cp−/− | Iron accumulation in hepatocytes and macrophages | Aceruloplasminemia | (189, 211, 341) |
DMT1 (G185R) | mk (missense) | Systemic iron deficiency; impaired iron uptake from the duodenum and by erythroid precursors | ND | (52, 151, 320) |
Belgrade rat | ||||
Duodenal cytochrome B | Cybrd1−/− | Little impact | ND | (153) |
Feline leukemia virus receptor | Flvcr−/− | Macrocytic anemia | ND | (153) |
Ferrochelatase | FECHm1Pas | Microcytic hypochromic anemia & severe porphyria | ND | (279) |
FECH−/− | Homozygous state is embryonic lethal; Heterozygotes have decreased FECH activity and mild porphyria | ND | (284) | |
Ferroportin | Slc40a1 (missense) | Iron loading of Kupffer cells, high serum ferritin, low transferrin saturation | ND | (153) |
Fpn−/− | Increased iron absorption and overload | Hfe4 hemochromatosis | (124) | |
Frataxin | Fxn−/− with human mutant Fxn YAC constructs | Mitochondrial iron deposits; neurodegeneration; cardiomyopathy; embryonic lethal | Friedreich's ataxia | (10, 153) |
Fxn−/− | Embryonic lethal | NA | (153) | |
H-ferritina | Fth+/− | Elevated tissue and serum L-ferritin | ND | (147, 428) |
Haptoglobin | Hp−/− | Increased export of iron from duodenum to plasma | ND | (270, 293) |
Heme oxygenase 1 | Hmox1−/− | Anemia; low serum iron; tissue iron deposition | Hmox 1 deficiency | (354) |
Hemojuvelin | Hjv−/− | Increased body iron, decreased hepcidin | ND | (153) |
Hemopxin | Hx−/− | Increased CNS iron | ND | (153) |
Hepcidin | HAMP (transgene) | Iron deficiency; Anemia | NA | (261) |
Hepcidinb | Usf2−/− | Hepatocellular iron accumulation; decreased macrophage iron; increased Tf saturation | Juvenile hemochromatosis | (321) |
Hepcidin/HFE | Hfe−/− | Amelioration of hepatic iron loading relative to Hfe−/− mice; increased body iron; decreased hepcidin | NA | (321) |
HfeC282Y/C282 | ||||
HFEH63D/H63D | ||||
Hephaestin | sla (deletion) | Microcytic hypochromic anemia; impaired iron transfer from the duodenum | ND | (447) |
Hfe | Hfe−/− | Hepatocellular iron accumulation; decreased macrophage iron; increased Tf saturation | Hfe hemochromatosis | (484) |
HfeC282Y/C282Yc | ||||
Irp2 | Irp2−/− | Microcytic anemia; duodenal and hepatic iron loading | Pulmonary disease | (89, 163) |
Mitoferrin 1 | Mfrn1−/− | Severe anemia | ND | (153) |
Sec1511 | Hbd | Deficiency in Tf cycling | ND | (464) |
Slc25a37 | Mfrn1−/− | Embryonic lethal with profound anemia | Tumors or cancer of the prostate | (81) |
Smad4 | Smad4−/− (liver specific) | Increased body iron; decreased hepcidin | ND | (452) |
Steap3 | Steap3−/− | Congenital, hypochromic, microcytic anemia; elevated red cell zinc protoporphyrin; functional erythroid iron deficiency; Impaired ferriereductase activity | ND | (153, 279, 327) |
Nm1054 (deletion) | ||||
Tmprss6 (matriptase-2) | Tmprss6−/− | Microcytic anemia; low iron stores; low serum iron; increased hepcidin | ND | (128) |
Tmprss6msk/msk | ||||
Transferrin | Hpx | Microcytic hypochromic anemia; tissue iron deposition | Atransferrinemia | (434) |
Transferrin receptor-1d | TfR+/− | Microcytic hypochromic erythrocytes; decreased iron stores; embryonic death | ND | (264) |
Transferrin receptor-2 | TfRr2246x/246 | Hepatocellular iron accumulation; decreased macrophage iron; increased Tf saturation | TfR2 hemochromatosis | (125, 152, 222) |
TfR2−/− | ||||
Transferrin | Tfhpx/hpx | Severe anemia, iron overload | Congenital hypotransferrinemia | (153) |
Fth−/− mice: early embryonic lethality.
Includes deletion of gene for upstream stimulatory factor-2.
Mutation is in mouse codon 294.
Tf−/− mice: embryonic lethal by E 12.5.
ND, not described; NA, not applicable; BMP, bone morphogenetic protein; Cp, ceruloplasmin; DMT1, divalent metal transporter 1; FECH, ferrochelatase; Fxn, frataxin; HFE, hereditary hemochromatosis gene product; Hp, hephaestin; Hpx, hemopexin; Irp1/Irp2, iron regulatory proteins 1 and 2; Tf, transferrin; TfR, transferrin receptor.