The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.
Microcytic anaemia mice have a mutation in Nramp2, a candidate iron transporter gene
Abstract
Although disorders of iron metabolism are prevalent, iron transport remains poorly understood. To address this problem, we undertook a positional cloning strategy to identify the causative mutation in mice with microcytic anaemia (mk). Homozygous mk/mk mice have microcytic, hypochromic anaemia due to severe defects in intestinal iron absorption and erythroid iron utilization. We report the identification of a strong candidate gene for mk, and suggest that the phenotype is a consequence of a missense mutation in Nramp2 (ref. 5), a previously identified gene of unknown function. Nramp2 is homologous to Nramp1, a gene activa in host defense. If Nramp2 is mk, as the cumulative evidence suggests, our findings have broad implications for the understanding of iron transport and resistance to intracellular pathogens.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“The freed ferric iron is then reduced to its bio-active ferrous form, Fe2+ by the ferrireductase STEAP3 (six-transmembrane epithelial antigen of prostate 3) and shuttled into the cytosol from the endosome by DMT1 (Fleming et al., 1997; Gunshin et al., 1997; Ohgami et al., 2005; Figure 1).”
From The Role of Iron Regulation in Immunometabolism and Immune-Related Disease (2019) · cites this paper as Fleming et al., 1997
In the citing paper
“However, inorganic iron uptake from the gastrointestinal lumen by enterocytes depends upon the divalent metal transporter protein 1 (DMT1 or NRAMP2), which is not able to import Fe3+. 12 , 13 , 14”
From The battle for iron in enteric infections (2020) · cites this paper as [12]
In the citing paper
“Liberated inorganic iron is then reduced by the ferrireductase STEAP3 to Fe 2ϩ , 10 which is the substrate for transmembrane transport by divalent metal transporter 1 (DMT1 or SLC11A2, formerly called NRAMP2, DCT1).”
From Forging a field: the golden age of iron biology. (2008) · cites this paper as [12]
In the citing paper
“In spite of these obstacles and entirely by chance, the first mammalian transmembrane iron transporter was discovered simultaneously in 2 laboratories, located within a city block of each other in Boston, using singularly modern techniques.12,13”
From Forging a field: the golden age of iron biology. (2008) · cites this paper as [12]
In the citing paper
“Interestingly, the clinical phenotype of patients with DMT1 mutations differs slightly from the corresponding mouse model, mk. 12”
From Forging a field: the golden age of iron biology. (2008) · cites this paper as [12]
In the citing paper
“Unlike TfR1, TfR2 does not contain an IRE in its mRNA and does not appear to be regulated in an iron-dependent manner (90, 315).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [90]
In the citing paper
“Studies of TfR2 expression in a mouse model for hemochromatosis revealed that TfR2 was not downregulated in conditions of iron overload (90), supporting the absence of an iron-mediated posttranscriptional regulatory mechanism.”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [90]
In the citing paper
“Interestingly, iron accumulation in the liver in type 1 HH results in the downregulation of TfR1, but in the case of TfR2, it is continually expressed even during HH-mediated iron loading (90).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [90]
In the citing paper
“In addition, TfR2 does not appear to be regulated by iron concentrations, for it lacks IRE in its mRNA and is not inducible by iron deficiency (90).”
From Intracellular iron transport and storage: from molecular mechanisms to health implications (2008) · cites this paper as [90]
Citations
Cites
Goffeau, A., Barrell, B. G., Bussey, H., Davis, R. W., Dujon, B., Feldmann, H., Galibert, F., Hoheisel, J. D., Jacq, C., Johnston, M., et al. (1996) · Science · doi:10.1126/science.274.5287.546 · Cited by 4,423
Friedreich's Ataxia: Autosomal Recessive Disease Caused by an Intronic GAA Triplet Repeat Expansion
Campuzano, V., Montermini, L., Moltò, M. D., Pianese, L., Cossée, M., Cavalcanti, F., Monros, E., Rodius, F., Duclos, F., Monticelli, A., et al. (1996) · Science · doi:10.1126/science.271.5254.1423 · Cited by 2,786
DNA methylation and the frequency of CpG in animal DNA
Bird, A. P. (1980) · Nucleic Acids Research · doi:10.1093/nar/8.7.1499 · Cited by 1,175
The I.M.A.G.E. Consortium: An Integrated Molecular Analysis of Genomes and Their Expression
Lennon, G., Auffray, C., Polymeropoulos, M. H., & Soares, M. B. (1996) · Genomics · doi:10.1006/geno.1996.0177 · Cited by 1,123
Natural resistance to infection with intracellular parasites: isolation of a candidate for Bcg
Vidal, S. M., Malo, D., Vogan, K., Skamene, E., & Gros, P. (1993) · Cell · doi:10.1016/0092-8674(93)90135-d · Cited by 1,104
Harding, A. E. (1981) · Brain · doi:10.1093/brain/104.3.589 · Cited by 929
Homozygosity Mapping: A Way to Map Human Recessive Traits with the DNA of Inbred Children
Lander, E. S., & Botstein, D. (1987) · Science · doi:10.1126/science.2884728 · Cited by 885
The FET3 gene of S. cerevisiae encodes a multicopper oxidase required for ferrous iron uptake.
Askwith, C., Eide, D., Van Ho, A., Bernard, P. S., Li, L., Davis-Kaplan, S., Sipe, D. M., & Kaplan, J. (1994) · Cell · doi:10.1016/0092-8674(94)90346-8 · Cited by 670
Dancis, A., Yuan, D. S., Haile, D., Askwith, C., Eide, D., Moehle, C., Kaplan, J., & Klausner, R. D. (1994) · Cell · doi:10.1016/0092-8674(94)90345-x · Cited by 659
Vidal, S., Tremblay, M. L., Govoni, G., Gauthier, S., Sebastiani, G., Malo, D., Skamene, E., Olivier, M., Jothy, S., & Gros, P. (1995) · The Journal of experimental medicine · doi:10.1084/jem.182.3.655 · Cited by 603
Ouahchi, K., Arita, M., Kayden, H. J., Hentati, F., Hamida, M. B., Sokol, R. J., Arai, H., Inoue, K., Mandel, J., & Koenig, M. (1995) · Nature Genetics · doi:10.1038/ng0295-141 · Cited by 574
A Macintosh program for storage and analysis of experimental genetic mapping data
Manly, K. F. (1993) · Mammalian Genome · doi:10.1007/bf00357089 · Cited by 496
Studies of human, mouse and yeast homologues indicate a mitochondrial function for frataxin
Koutníková, H., Campuzano, V., Foury, F., Dollé, P., Cazzalini, O., & Koenig, M. (1997) · Nature Genetics · doi:10.1038/ng0897-345 · Cited by 473
Gruenheid, S., Pinner, E., Desjardins, M., & Gros, P. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.185.4.717 · Cited by 428
Goffeau, A., Aert, R., Agostini-Carbone, M. L., Ahmed, A., Aigle, M., Alberghina, L., Albermann, K., Albers, M., Aldea, M., Alexandraki, D., et al. (1997) · Nature · doi:10.1038/387s005 · Cited by 412
Nramp defines a family of membrane proteins.
Cellier, M. F., Privé, G. G., Belouchi, A., Kwan, T., Rodrigues, V., Chia, W., & Gros, P. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.22.10089 · Cited by 352
Respiratory deficiency due to loss of mitochondrial DNA in yeast lacking the frataxin homologue
Wilson, R. B., & Roof, D. M. (1997) · Nature Genetics · doi:10.1038/ng0897-352 · Cited by 345
Supek, F., Supekova, L., Nelson, H., & Nelson, N. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.10.5105 · Cited by 325
Mapping of mutation causing Friedreich's ataxia to human chromosome 9
Chamberlain, S., Shaw, J., Rowland, A., Wallis, J., South, S., Nakamura, Y., von Gabain, A., Farrall, M., & Williamson, R. (1988) · Nature · doi:10.1038/334248a0 · Cited by 317
Identification and characterization of a second mouse Nramp gene
Gruenheid, S., Cellier, M. F., Vidal, S. M., & Gros, P. (1995) · Genomics · doi:10.1016/0888-7543(95)80053-o · Cited by 287
Friedreich's ataxia protein: phylogenetic evidence for mitochondrial dysfunction
Gibson, T. J., Koonin, E. V., Musco, G., Pastore, A., & Peer Bork, B. (1996) · Trends in Neurosciences · doi:10.1016/s0166-2236(96)20054-2 · Cited by 159
Rodrigues, V., Cheah, P. Y., Ray, K., & Chia, W. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb07303.x · Cited by 136
Resistance to intracellular infections: comparative genomic analysis of Nramp
Cellier, M. F., Belouchi, A., & Gros, P. (1996) · Trends in Genetics · doi:10.1016/0168-9525(96)30042-5 · Cited by 125
Interrelation of intestinal transport system for manganese and iron.
Thomson, A. B. R., Olatunbosun, D. A., & Valverg, L. S. (1971) · PubMed · Cited by 123
Defect of Intestinal Mucosal Iron Uptake in Mice with Hereditary Microcytic Anemia
Edwards, J. A., & Hoke, J. E. (1972) · Experimental Biology and Medicine · doi:10.3181/00379727-141-36720 · Cited by 79
West, A. H., Clark, D. J., Martin, J., Neupert, W., Hartl, F. U., & Horwich, A. L. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)35810-1 · Cited by 72
Natural resistance to infection with intracellular parasites: isolation of a candidate for Bcg
Vidal, S. M. (1993) · Trends in Genetics · doi:10.1016/0168-9525(93)90008-6 · Cited by 58
Red cell iron uptake in hereditary microcytic anemia
Edwards, J., & Hoke, J. (1975) · Blood · doi:10.1182/blood.v46.3.381.381 · Cited by 53
Characterization and genetic studies of microcytic anemia in house mouse.
RUSSELL, E. S., NASH, D. J., BERNSTEIN, S. E., KENT, E. L., MCFARLAND, E. C., MATTHEWS, S. M., & NORWOOD, M. S. (1970) · Blood · doi:10.1182/blood.v35.6.838.838 · Cited by 51
Friedreich's Ataxia 1980 An Overview of the Physiopathology
Barbeau, A. (1980) · Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · doi:10.1017/s0317167100023064 · Cited by 38
Marrow Transplantation and Iron Therapy in Mouse Hereditary Microcytic Anemia
Harrison, D. E. (1972) · Blood · doi:10.1182/blood.v40.6.893.893 · Cited by 37
Low viability, skin lesions, and reduced fertility associated with microcytic anemia in the mouse.
Russell, E. S., McFarland, E. C., & KENT, E. L. (1970) · PubMed · Cited by 26
Mitochondrial dysfunction and spinocerebellar degenerations
Cedarbaum, J. M., & Blass, J. P. (1986) · Neurochemical Pathology · doi:10.1007/bf02834298 · Cited by 25
Mitochondrial myopathies: genetic defects
Harding, A. E., Holt, I. J., Cooper, J. A. D., Schapira, A. H. V., Sweeney, M. G., Clark, J. B., & MORGAN-HUGHES, J. A. (1990) · Biochemical Society Transactions · doi:10.1042/bst0180519 · Cited by 22
Handa, S., Ferguson, J. M., Wallace, M. E., & Bulfield, G. (1988) · Genetics Research · doi:10.1017/s0016672300023922 · Cited by 8
Flagged first, then by citations
Research works printed but not linked: 2
- McFarland, E.C. & Russell, E.S. Microcytic anemia (mk) has been located close to Ca on chromosome 15. Mouse News Letter 53, 35 (1975).
- Weinberg, E.D. The iron-withholding defense system. ASM News 59, 559–562 (1993).
Cited by
Sorted by citations
Ferroptosis turns 10: Emerging mechanisms, physiological functions, and therapeutic applications
Stockwell, B. R. (2022) · Cell · doi:10.1016/j.cell.2022.06.003 · Cited by 3,211
Andrews, N. C. (1999) · New England Journal of Medicine · doi:10.1056/nejm199912233412607 · Cited by 2,130
Self-citationHentze, M. W., Muckenthaler, M. U., & Andrews, N. C. (2004) · Cell · doi:10.1016/s0092-8674(04)00343-5 · Cited by 1,736
Self-citationPositional cloning of zebrafish ferroportin1 identifies a conserved vertebrate iron exporter
Donovan, A., Brownlie, A., Zhou, Y., Shepard, J., Pratt, S. J., Moynihan, J., Paw, B. H., Drejer, A., Barut, B., Zapata, A., et al. (2000) · Nature · doi:10.1038/35001596 · Cited by 1,667
Self-citationHepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation
Ganz, T. (2003) · Blood · doi:10.1182/blood-2003-03-0672 · Cited by 1,544
Metadata
- Authors
- Fleming, M. D., Trenor, C. C., Su, M. A., Foernzler, D., Beier, D. R., Dietrich, W. F., & Andrews, N. C.
- Affiliations
- Brigham and Women's Hospital (US)
- Boston Children's Hospital (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Andrews, Nancy C.
- Venue
- Nature Genetics
- Published
- 1997-08
- Volume
- 16
- Issue
- 4
- Pages
- 383-386
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2082806735
- Cited by
- 1,159
- References
- 35
- Citations by year
- 2026: 7 · 2025: 13 · 2024: 11 · 2023: 16 · 2022: 12 · 2021: 14 · 2020: 13 · 2019: 23 · 2018: 20 · 2017: 23 · 2016: 21 · 2015: 24 · 2014: 28 · 2013: 33 · 2012: 35
- FWCI
- 42.97
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- Funders
- National Institutes of Health (1k08hl003600-01)
- National Heart, Lung, and Blood Institute (K08 HL03600)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Keywords
- microcytic anemia, DMT1, iron transport, iron metabolism, intestinal iron absorption, missense mutations, positional cloning, NRAMP1, mice
- MeSH terms
- Frataxin, Animals, Friedreich Ataxia, Humans, Mitochondria, Phosphotransferases (Alcohol Group Acceptor), Iron-Binding Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
