The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.
Transferrin receptor 2: Continued expression in mouse liver in the face of iron overload and in hereditary hemochromatosis
Open accessAbstract
Hereditary hemochromatosis (HH) is a common autosomal recessive disorder characterized by excess absorption of dietary iron and progressive iron deposition in several tissues, particularly liver. Liver disease resulting from iron toxicity is the major cause of death in HH. Hepatic iron loading in HH is progressive despite down-regulation of the classical transferrin receptor (TfR). Recently a human cDNA highly homologous to TfR was identified and reported to encode a protein (TfR2) that binds holotransferrin and mediates uptake of transferrin-bound iron. We independently identified a full-length murine EST encoding the mouse orthologue of the human TfR2. Although homologous to murine TfR in the coding region, the TfR2 transcript does not contain the iron-responsive elements found in the 3′ untranslated sequence of TfR mRNA. To determine the potential role for TfR2 in iron uptake by liver, we investigated TfR and TfR2 expression in normal mice and murine models of dietary iron overload (2% carbonyl iron), dietary iron deficiency (gastric parietal cell ablation), and HH (HFE −/−). Northern blot analyses demonstrated distinct tissue-specific patterns of expression for TfR and TfR2, with TfR2 expressed highly only in liver where TfR expression is low.In situ hybridization demonstrated abundant TfR2 expression in hepatocytes. In contrast to TfR, TfR2 expression in liver was not increased in iron deficiency. Furthermore, hepatic expression of TfR2 was not down-regulated with dietary iron loading or in the HFE −/− model of HH. From these observations, we propose that TfR2 allows continued uptake of Tf-bound iron by hepatocytes even after TfR has been down-regulated by iron overload, and this uptake contributes to the susceptibility of liver to iron loading in HH.
Overview
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
Cites
Statistics
Verification
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.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Molecular Cloning of Transferrin Receptor 2
Kawabata, H., Yang, R., Hirama, T., Vuong, P. T., Kawano, S., Gombart, A. F., & Koeffler, H. P. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.30.20826 · Cited by 650
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
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 521
Self-citationMolecular medicine and hemochromatosis: At the crossroads
Bacon, B. R., Powell, L. W., Adams, P. C., Kresina, T. F., & Hoofnagle, J. H. (1999) · Gastroenterology · doi:10.1016/s0016-5085(99)70244-1 · Cited by 286
Self-citationFleming, R. E., Migas, M. C., Zhou, X., Jiang, J., Britton, R. S., Brunt, E. M., Tomatsu, S., Waheed, A., Bacon, B. R., & Sly, W. S. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.6.3143 · Cited by 269
Self-citationThe C282Y Mutation Causing Hereditary Hemochromatosis Does Not Produce a Null Allele
Levy, J. E., Montross, L. K., Cohen, D. E., Fleming, M. D., & Andrews, N. C. (1999) · Blood · doi:10.1182/blood.v94.1.9.413a43_9_11 · Cited by 260
Diphtheria Toxin-mediated Ablation of Parietal Cells in the Stomach of Transgenic Mice
Li, Q., Karam, S. M., & Gordon, J. I. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.7.3671 · Cited by 202
Characterization of non-transferrin-bound iron clearance by rat liver.
Wright, T. L., Brissot, P., Ma, W. L., & Weisiger, R. A. (1986) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)67473-3 · Cited by 197
Bonkovsky, H. L. (1991) · The American Journal of the Medical Sciences · doi:10.1097/00000441-199101000-00006 · Cited by 192
Quantification of Non-Transferrin-Bound Iron in the Presence of Unsaturated Transferrin
Gosriwatana, I., Loreal, O., Lu, S., Brissot, P., Porter, J., & Hider, R. C. (1999) · Analytical Biochemistry · doi:10.1006/abio.1999.4216 · Cited by 168
Cited by
Targeted Drug Delivery via the Transferrin Receptor-Mediated Endocytosis Pathway
Qian, Z. M., Li, H., Sun, H., & Ho, K. (2002) · Pharmacological Reviews · doi:10.1124/pr.54.4.561 · Cited by 1,019
Hereditary Hemochromatosis — A New Look at an Old Disease
Pietrangelo, A. (2004) · New England Journal of Medicine · doi:10.1056/nejmra031573 · Cited by 992
Chemistry and biology of eukaryotic iron metabolism
Aisen, P. (2001) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/s1357-2725(01)00063-2 · Cited by 804
The gene TFR2 is mutated in a new type of haemochromatosis mapping to 7q22
Camaschella, C., Roetto, A., Calì, A., De Gobbi, M., Garozzo, G., Carella, M., Majorano, N., Totaro, A., & Gasparini, P. (2000) · Nature Genetics · doi:10.1038/75534 · Cited by 803
Intracellular iron transport and storage: from molecular mechanisms to health implications
Mackenzie, E. L., Iwasaki, K., & Tsuji, Y. (2008) · Antioxidants & Redox Signaling · doi:10.1089/ars.2007.1893 · Cited by 526
Metadata
- Authors
- Fleming, R. E., Migas, M. C., Holden, C. C., Waheed, A., Britton, R. S., Tomatsu, S., Bacon, B. R., & Sly, W. S.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2000-02-18
- Volume
- 97
- Issue
- 5
- Pages
- 2214-2219
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2005523979
- Cited by
- 273
- References
- 35
- FWCI
- 13.44
- Type
- journal article
- Language
- en
- Open access
- green
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
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Transferrin receptor 2: Continued expression in mouse liver in the face of iron overload and in hereditary hemochromatosis. https://app.cochat.ai/papers/10.1073/pnas.040548097
- The paper
- Fleming, R. E., Migas, M. C., Holden, C. C., Waheed, A., Britton, R. S., Tomatsu, S., Bacon, B. R., & Sly, W. S. (2000). Transferrin receptor 2: Continued expression in mouse liver in the face of iron overload and in hereditary hemochromatosis. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.040548097
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
