ArticleProceedings of the National Academy of Sciences of the United States of America2002
Targeted mutagenesis of the murine transferrin receptor-2 gene produces hemochromatosis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
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Who cites it
85 citing papers in PubMed, 241 citations in OpenAlex.
- Mechanisms of Thrombocytosis in Iron-Deficiency Anemia.European journal of haematology · 2026Review
- Application of Cumulative Threshold Approaches to Tissue Iron Measurement on Histochemical or Synchrotron X‑ray Fluorescence Platforms.Chemical & biomedical imaging · 2026Article
- Transferrin receptors.Experimental & molecular medicine · 2025Review
- Transferrin Receptor 2 in Canine Testicular Tumors: An Emerging Key Role in Seminomas.Animals : an open access journal from MDPI · 2025Article
- Editorial: The potential of transferrin as a drug target and drug delivery system.Frontiers in pharmacology · 2025Article
- Lack of Hfe and TfR2 in Macrophages Impairs Iron Metabolism in the Spleen and the Bone Marrow.International journal of molecular sciences · 2024Article
- Iron metabolism and ferroptosis in diabetic bone loss: from mechanism to therapy.Frontiers in nutrition · 2023Review
- Functional role of endothelial transferrin receptor 1 in iron sensing and homeostasis.American journal of hematology · 2022Article
- Article
- Effects of Exogenous Transferrin on the Regulation of Iron Metabolism and Erythropoiesis in Iron Deficiency With or Without Anemia.Frontiers in physiology · 2022Article
- New Mutations inGenes · 2021Article
- Evaluation of the Association of Transferrin Receptor Type 2 Gene Mutation (Y250X) with Iron Overload in Major β- Thalassemia.Archives of Razi Institute · 2021Article
- The Role of Iron in Benign and Malignant Hematopoiesis.Antioxidants & redox signaling · 2021Review
- Effect of Erythropoietin on the Expression of Murine Transferrin Receptor 2.International journal of molecular sciences · 2021Article
- HFE Gene Variants' Impact on Anthracycline-Based Chemotherapy-Induced Subclinical Cardiotoxicity.Cardiovascular toxicology · 2021Article
- Extrahepatic deficiency of transferrin receptor 2 is associated with increased erythropoiesis independent of iron overload.The Journal of biological chemistry · 2020Article
- Iron Overload Mimicking Conditions Skews Bone Marrow Dendritic Cells Differentiation into MHCIIInternational journal of molecular sciences · 2020Article
- Animal Models of Normal and Disturbed Iron and Copper Metabolism.The Journal of nutrition · 2019Review
- Lobe specificity of iron binding to transferrin modulates murine erythropoiesis and iron homeostasis.Blood · 2019Article
- Transferrin receptor 2 controls bone mass and pathological bone formation via BMP and Wnt signaling.Nature metabolism · 2019Article
25 more citing papers are in PubMed but not listed here.
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9 authors at 2 institutions in 1 country.
Funding
Abstract
Hereditary hemochromatosis (HH) is a common genetic disorder characterized by excess absorption of dietary iron and progressive iron deposition in several tissues, particularly liver. The vast majority of individuals with HH are homozygous for mutations in the HFE gene. Recently a second transferrin receptor (TFR2) was discovered, and a previously uncharacterized type of hemochromatosis (HH type 3) was identified in humans carrying mutations in the TFR2 gene. To characterize the role for TFR2 in iron homeostasis, we generated mice in which a premature stop codon (Y245X) was introduced by targeted mutagenesis in the murine Tfr2 coding sequence. This mutation is orthologous to the Y250X mutation identified in some patients with HH type 3. The homozygous Tfr2(Y245X) mutant mice showed profound abnormalities in parameters of iron homeostasis. Even on a standard diet, hepatic iron concentration was several-fold higher in the homozygous Tfr2(Y245X) mutant mice than in wild-type littermates by 4 weeks of age. The iron deposition in the mutant mice was predominantly hepatocellular and periportal. The mean splenic iron concentration in the homozygous Tfr2(Y245X) mutant mice was significantly less than that observed in the wild-type mice. The homozygous Tfr2(Y245X) mutant mice also demonstrated elevated transferrin saturations. There were no significant differences in parameters of erythrocyte production including hemoglobin levels, hematocrits, erythrocyte indices, and reticulocyte counts. Heterozygous Tfr2(Y245X) mice did not differ in any measured parameter from wild-type mice. This study confirms the important role for TFR2 in iron homeostasis and provides a tool for investigating the excess iron absorption and abnormal iron distribution in iron-overload disorders.
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