Cited by 568Iron Metabolism and DisordersNeurological diseases and metabolismTrace Elements in Health

The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.

Targeted gene disruption reveals an essential role for ceruloplasmin in cellular iron efflux

Open access

Harris, Z. Leah, Durley, Alison P., Man, Tsz Kwong, Gitlin, Jonathan D.·1999·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.96.19.10812PMC PMC17965

Open this paper in CoChat — free account

Abstract

Aceruloplasminemia is an autosomal recessive disorder of iron metabolism. Affected individuals evidence iron accumulation in tissue parenchyma in association with absent serum ceruloplasmin. Genetic studies of such patients reveal inherited mutations in the ceruloplasmin gene. To elucidate the role of ceruloplasmin in iron homeostasis, we created an animal model of aceruloplasminemia by disrupting the murine ceruloplasmin ( Cp ) gene. Although normal at birth, Cp −/− mice demonstrate progressive accumulation of iron such that by one year of age all animals have a prominent elevation in serum ferritin and a 3- to 6-fold increase in the iron content of the liver and spleen. Histological analysis of affected tissues in these mice shows abundant iron stores within reticuloendothelial cells and hepatocytes. Ferrokinetic studies in Cp +/+ and Cp −/− mice reveal equivalent rates of iron absorption and plasma iron turnover, suggesting that iron accumulation results from altered compartmentalization within the iron cycle. Consistent with this concept, Cp −/− mice showed no abnormalities in cellular iron uptake but a striking impairment in the movement of iron out of reticuloendothelial cells and hepatocytes. Our findings reveal an essential physiologic role for ceruloplasmin in determining the rate of iron efflux from cells with mobilizable iron stores.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1073/pnas.96.19.10812

Cites

40 of 40 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

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?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cloning and characterization of a mammalian proton-coupled metal-ion transporter
Gunshin, H., Mackenzie, B., Berger, U. V., Gunshin, Y., Romero, M. F., Boron, W. F., Nussberger, S., Gollan, J. L., & Hediger, M. A. (1997) · Nature · doi:10.1038/41343 · Cited by 3,166
Neonatal lethality and lymphopenia in mice with a homozygous disruption of the c-abl proto-oncogene
Tybulewicz, V. L. J., Crawford, C. E., Jackson, P. K., Bronson, R. T., & Mulligan, R. C. (1991) · Cell · doi:10.1016/0092-8674(91)90011-m · Cited by 1,281
Microcytic anaemia mice have a mutation in Nramp2, a candidate iron transporter gene
Fleming, M. D., Trenor, C. C., Su, M. A., Foernzler, D., Beier, D. R., Dietrich, W. F., & Andrews, N. C. (1997) · Nature Genetics · doi:10.1038/ng0897-383 · Cited by 1,159
Hephaestin, a ceruloplasmin homologue implicated in intestinal iron transport, is defective in the sla mouse
Vulpe, C. D., Kuo, Y.-M., Murphy, T. L., Cowley, L., Askwith, C., Libina, N., Gitschier, J., & Anderson, G. J. (1999) · Nature Genetics · doi:10.1038/5979 · Cited by 1,084
Heme oxygenase 1 is required for mammalian iron reutilization
Poss, K. D., & Tonegawa, S. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.20.10919 · Cited by 1,016
Regulation of Mitochondrial Iron Accumulation by Yfh1p, a Putative Homolog of Frataxin
Babcock, M., de Silva, D., Oaks, R., Davis-Kaplan, S., Jiralerspong, S., Montermini, L., Pandolfo, M., & Kaplan, J. (1997) · Science · doi:10.1126/science.276.5319.1709 · Cited by 921
The possible significance of the ferrous oxidase activity of ceruloplasmin in normal human serum.
Osaki, S., Johnson, D. A., & Frieden, E. (1966) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)96527-0 · Cited by 679
Transferrin receptor is necessary for development of erythrocytes and the nervous system
Levy, J. E., Jin, O., Fujiwara, Y., Kuo, F., & Andrews, N. (1999) · Nature Genetics · doi:10.1038/7727 · Cited by 574
Aceruloplasminemia: molecular characterization of this disorder of iron metabolism.
Harris, Z. L., Takahashi, Y., Miyajima, H., Serizawa, M., MacGillivray, R. T., & Gitlin, J. D. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.7.2539 · Cited by 558
Self-citation
HFE gene knockout produces mouse model of hereditary hemochromatosis
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., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.5.2492 · Cited by 519

Show all 40 references

Research works printed but not linked: 4

P Ponka, C Beaumont, D R Richardson Semin Hematol 35, 35–54 (1998).
B R Bacon, M L Schilsky Adv Intern Med 44, 91–116 (1999).
J I Logan, K B Harveyson, G B Wisdom, A E Hughes, G P R Archbold Q J Med 87, 663–670 (1994).
J D Torrance, T H Bothwell Methods in Hematology: Iron, ed J D Cook (Churchill Livingstone, New York), pp. 104–109 (1980).

Sorted by citations

Items 501–567 of 567

Iron and Copper Metabolism in the Myelodysplastic Syndromes
Várkonyi, J., Bekő, G., Prohászka, Z., & Karádi, I. (2011) · Springer eBooks · doi:10.1007/978-94-007-0440-4_11 · Cited by 1
Iron in mammals: pathophysiological mechanisms of overload and deficiency in relation to disease
Johnson, M. B., Enns, C. A., & Zhang, A. (2005) · Topics in current genetics · doi:10.1007/4735_99 · Cited by 1
Disorders of Iron Overload
Pietrangelo, A., & Torbenson, M. S. (2023) · Elsevier eBooks · doi:10.1016/b978-0-7020-8228-3.00004-1 · Cited by 1
Prevalência das mutações C282y e H63D no gene da hemocromatose hereditária (HFE) em pacientes com diabetes melito tipo 2 e a sua relação com as complicações crônicas
Colli, M. L. (2007) · Americanae (AECID Library) · Cited by 1
The role of peripheral blood mononuclear cells in atherogenesis
Bispo, C. (2011) · Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) · Cited by 1
Post-transcriptional regulation of HFE gene expression
Martins, R. (2011) · Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) · Cited by 1
Molecular mechanism of regulation of iron transport across placenta
Hanif, R. (2012) · UCL Discovery (University College London) · Cited by 1
Obesity and cardiovascular disease. Aspects of methods and susceptibility.
Calling, S. (2006) · Lund University Publications (Lund University) · Cited by 1
How are genes measured? Examples from studies on iron metabolism in pregnancy
Andersen, H. S., & McArdle, H. J. (2004) · Proceedings of The Nutrition Society · doi:10.1079/pns2004368 · Cited by 1
Mutation analysis of four genes implicated in iron homeostasis in porphyria cutanea tarda (PCT) patients
Panton, N. (2008) · SUNScholar (Stellenbosch University) · Cited by 1
Characterization of glycosylphoshatidylinositol-anchored ceruloplasmin in multiple redent organs following dietary copper deficiency.
Mostad, E. (2010) · University of Minnesota Digital Conservancy (University of Minnesota) · Cited by 1
[The molecular genetics of hematochromatosis].
Rosmorduc, O., Hermelin, B., & Poupon, R. Y. (2002) · PubMed · Cited by 1
Molecular regulation of iron homeostasis and resistance to infection in alcoholics
Barry, J. P. (2002) · Frontiers in bioscience · doi:10.2741/potter · Cited by 1
Mechanisms of Copper Deficiency in the Zebrafish Embryo
Madsen, E. C. (2010) · PubMed Central · doi:10.7936/k79c6vdt
Differential Regulation of Ceruloplasmin Isoforms Expression in Macrophages and Hepatocytes
Marques, L., Auriac, A., Willemetz, A., Banha, J., da Silva, B. D. C. F. L., Canonne‐Hergaux, F., & Costa, L. M. G. (2011) · Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT)
Miscellaneous Iron-Related Disorders
Beaumont, C. (2011) · Humana Press eBooks · doi:10.1007/978-1-60327-485-2_21
Ferroportin 1 expression regulates intracellular growth of Salmonella enterica serovar Typhimurium, a link between innate immunity and hereditary hemochromatosis
Chlosta, S. (2008) · Universitätsbibliothek der FU Berlin Hochschulschriftenstelle u. Dokumentenserver · doi:10.17169/refubium-18022
BEHIND THE IRON CURTAIN: DEXRAS1 MEDIATES GLUTAMATEN-MDA INDUCED NEURONAL IRON UPTAKE
Cheah, J. H. (2006)
Micronutrients, Trace Elements
Cousins, R. J. (2006) · Wiley-VCH eBooks · doi:10.1002/3527600906.mcb.200400037
IRON HOMEOSTASIS IN IMMUNE MONONUCLEAR CELLS: A POTENTIAL ROLE IN ATHEROGENESIS
Marques, L. (2015) · Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) · doi:10.13140/rg.2.2.24210.40643
Mammalian Models of Iron Homeostasis
Britton, R. S., Bacon, B. R., & Fleming, R. E. (2011) · Humana Press eBooks · doi:10.1007/978-1-60327-485-2_29
Dietary factors influencing non-heme iron absorption
Bonsmann, S. S. G. (2007) · Repository for Publications and Research Data (ETH Zurich) · doi:10.3929/ethz-a-005332658
Efeitos do Sulforafano sobre a disfunção cognitiva induzida pelo acúmulo de ferro cerebral
Lavich, I. C. (2015) · LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas)
Analysis of genes implicated in iron regulation in individuals presenting with primary iron overload in the South African population
Booley, F. (2007) · SUNScholar (Stellenbosch University)
Effect of Copper on the Regulation of Ferroportin-1 Gene Expression
Park, B.-Y., & Chung, J. (2009) · Journal of Nutrition and Health · doi:10.4163/kjn.2009.42.5.434
Mix 'n' match metalloproteins
Fox, P. L. (2004) · Blood · doi:10.1182/blood-2004-04-1287
Aceroluplasminemia, una nueva enfermedad por acumulación de hierro
Pérez-Aguilar, F. (2002) · Gastroenterología y Hepatología · doi:10.1016/s0210-5705(02)70247-1
Regulation of hepcidin and hemojuvelin expression and their role in iron homeostasis
Salama, M. (2010) · UCL Discovery (University College London)
Mutations du gène HFE dans le cancer épithélial de l'ovaire
Medelci, S. (2008) · doi:10.71781/31650
Iron: Molecular Basis of Hemochromatosis
Schmidt, P. J. (2004) · Wiley eBooks · doi:10.1002/9781119951438.eibc2137
Review The role of hepcidin and ferroportin in iron absorption
Oates, P. S. (2007)
Mécanismes de l'homéostasie
Beaumont, C. (2004)
Running title: Iron assimilation in Chlamydomonas
Allen, M. D., Campo, J. A. D., Kropat, J., & Merchant, S. (2007)
Studies on the role of hephaestin and transferrin in iron transport
Hudson, D. M. (2008) · cIRcle (University of British Columbia) · doi:10.14288/1.0066537
Hypoxia-Dependent Hepcidin Down-Regulation: In Vitro and In Vivo Studies
Ravasi, G. (2016) · BOA (University of Milano-Bicocca)
The molecular mechanism for interaction of ceruloplasmin and myeloperoxidase
Bakhautdin, B., & Bakhautdin, E. G. (2016) · AIP conference proceedings · doi:10.1063/1.4945844
Iron Transporters and Iron Homeostasis
Knutson, M. D. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-802168-2.00018-x
The Prognostic Capability and Molecular Function of Duodenal Cytochrome B in Breast Cancer
Lemler, D. J. (2016) · OpenCommons at University of Connecticut (University of Connecticut)
Utjecaj sistemske upale na homeostazu željeza u egzacerbaciji i stabilnoj fazi kronične opstrukcijske plućne bolesti
Tandara, L. (2016) · Repozitorij Farmaceutsko-biokemijskog fakulteta (Sveučilišta u Zagrebu)
Processing and trafficking of the iron regulatory protein, hemojuvelin
Maxson, J. E. (2014) · doi:10.6083/m4t43r2s
Regulation of transferrin receptor 2 stability and trafficking in hepatoma cells
Johnson, M. B. (2006) · doi:10.6083/m4wm1bpk
BRAIN IRON DEFICIENCY IN HUMANS AND ANIMAL MODELS
Clardy, S. L. (2005)
Elucidating the role of Mitoferrin (Mfrn), Iron Regulatory Proteins (IRP1 and IRP2) and Hephaestin (Heph) in iron metabolism by tagSNP and Protein-Protein Interaction (PPI) analysis
Velaga, R. M. (2014) · London Met Repository (London Metropolitan University)
Surcharges en fer génétiques : atypies de l’acéruloplasminémie héréditaire
Loréal, O. (2019) · Bulletin de l Académie Nationale de Médecine · doi:10.1016/j.banm.2019.05.013
Evaluation of process parameters used in the non-aqueous anodization of aluminum alloys
Panitz, J. K. G., Sharp, D. J., & Peterson, D. E. (1982) · OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information)
Ceruloplasmin
Eden, M. E. V., & Aust, S. D. (2002) · Wiley eBooks · doi:10.1002/0471203076.emm0217
Metalloneurochemistry
Nam, G., Yi, Y., Lee, H. J., Lee, J., Kang, J., & Lim, M. H. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-409547-2.14902-9
Hereditäre Lebererkrankungen
Lackner, C., & Knisely, A. S. (2020) · Pathologie · doi:10.1007/978-3-642-04557-8_4
Iron Proteins for Storage & Transport & Their Synthetic Analogs
Lewin, A. C., Brun, N. E. L., & Moore, G. R. (2005) · Encyclopedia of Inorganic Chemistry · doi:10.1002/0470862106.ia114
Iron
Saraf, S. L., & Gordeuk, V. R. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-805378-2.00006-1 · Cited by 1
Iron overload and the liver
Yin, J. L., Raja, K. B., & Ala, A. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-26711-6.00029-9
THE ROLE OF CERULOPLASMIN IN COLITIS
Bakhautdin, B. (2010) · EngagedScholarship @ Cleveland State University (Cleveland State University)
Determinants of iron, zinc, and copper concentrations in the hair of dogs and cats
Badea, E., GORAN, G. V., & Ţoca, C. (2026) · Journal of Trace Elements in Medicine and Biology · doi:10.1016/j.jtemb.2026.127826
The Dysregulation of Iron Homeostasis in Obesity
Ramasamy, J. (2025) · Springer eBooks · doi:10.1007/978-3-031-32047-7_115-1 · Cited by 1
Importance d'un complément associant le fer et la vitamine E dans le traitement de l'anémie ferriprive chez de jeunes enfants brésiliens
de Carvalho, A. G. C. (2010) · theses.fr (ABES) · doi:10.70675/3eef4184z1db5z47f0z8097z1a1424d1940b
Marqueurs biologiques du cuivre dans les maladies métaboliques du cuivre, notamment la maladie de Wilson : approche analytique et bio-clinique
Djebrani‐Oussedik, N. (2018) · theses.fr (ABES) · doi:10.70675/d9b346b4z5fffz44dczb940z00adef6986f1
Fer et autres métaux : interrelations métaboliques et rôle de l'hepcidine
Cavey, T. (2017) · theses.fr (ABES) · doi:10.70675/402f5b81z6d39z4031za866z25a316a87b2a
Caractérisation du phénotype hépatosplénique d'un nouveau modèle de rats acéruloplasminémiques pour une meilleure compréhension des mécanismes physiopathologiques de l'acéruloplasminémie héréditaire
Kenawi, M. (2019) · theses.fr (ABES) · doi:10.70675/dae51f55z039cz470czae8bz753d01043b36
La sérotonine intestinale : un acteur essentiel de la régulation de l'homéostasie du fer
Falabrègue, M. (2020) · theses.fr (ABES) · doi:10.70675/911bf09czfa11z4227zacfaz2f72ec7a7582
Le rôle de l'érythroferrone dans la régulation du métabolisme du fer
Sardo, U. (2020) · theses.fr (ABES) · doi:10.70675/d03e67aczc44bz4af9z8fa1zef080668f44f
Apport dans le métabolisme du fer du modèle murin macrophage autophagie déficient & relations fer - inflammation
Taleb, M. (2021) · theses.fr (ABES) · doi:10.70675/3fae5636z8e09z46ecza8d8zf84434d2bf14
Caractérisation et fonctions des macrophages alternatifs humains dans un contexte de maladies cardio-métaboliques
Bories, G. F. P. (2011) · theses.fr (ABES) · doi:10.70675/81757398zf42fz45dcz8424z3f14e050bfb4
L-DOPA influences transferrin-dependent iron release at the blood-brain barrier
Serpa, R. O., Palsa, K., Tufano, E., Laukhuff, H., Spiegelman, V. S., Elcheva, I. A., & Connor, J. R. (2026) · Fluids and Barriers of the CNS · doi:10.1186/s12987-026-00822-5
Diagnosis of de novo fetal aceruloplasminemia via whole exome sequencing and fetal umbilical blood ceruloplasmin measurement
Jin, P., Dai, G., Hong, J., Han, S., Wang, X., Guo, X., Hu, W., Qian, Y., Wang, Y., Zhang, J., et al. (2026) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-026-04445-9
Inherited microcytic anemias due to disorders of iron and heme metabolism: An updated clinical review
Makis, A. C., Saougou, I., & Hatzimichael, E. C. (2026) · HemaSphere · doi:10.1002/hem3.70465
The molecular basis of the interactions of copper metallochaperones
Aggarwal, S. (2011)
Analysis of the induction of the cytoprotective Nrf2 signalling pathway in reticuloendothelial cells from iron-treated mice and HFE Haemochromatosis patients
Sousa, F. F. D. (2012) · Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) · doi:10.34626/9qa6-4j32

Authors: Harris, Z. L., Durley, A. P., Man, T. K., & Gitlin, J. D.
Affiliations: Washington University in St. Louis (US)
ORCID: Harris, Z. Leah
Man, Tsz Kwong
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 1999-09-14
Volume: 96
Issue: 19
Pages: 10812-10817
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.96.19.10812
PMC: PMC17965
OpenAlex: W2104657893
Cited by: 568
References: 40
Citations by year: 2026: 6 · 2025: 3 · 2024: 10 · 2023: 13 · 2022: 16 · 2021: 17 · 2020: 20 · 2019: 17 · 2018: 20 · 2017: 14 · 2016: 17 · 2015: 14 · 2014: 18 · 2013: 13 · 2012: 24
FWCI: 15.54
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (1p30hd033688-01, 5r01hl041536-13, 5k08dk002464-04, DK02464, HL41536)
National Heart, Lung, and Blood Institute (HL41536)
National Institute of Diabetes and Digestive and Kidney Diseases (DK02464)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 33688)
Topics: Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
Keywords: ceruloplasmin, aceruloplasminemia, iron efflux, cellular iron homeostasis, iron accumulation, iron metabolism, ferrokinetics, reticuloendothelial cells, hepatocytes, serum ferritin, iron storage
MeSH terms: Animals, Apoproteins, Ceruloplasmin, Disease Models, Animal, Homeostasis, Iron, Liver, Metal Metabolism, Inborn Errors, Models, Genetic, Phenotype, Spleen, Time Factors, Mutagenesis, Insertional, Neurodegenerative Diseases, Mice

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

Targeted gene disruption reveals an essential role for ceruloplasmin in cellular iron efflux

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks