A critical role for murine transferrin receptor 2 in erythropoiesis during iron restriction

Wallace, Daniel F., Secondes, Eriza S., Rishi, Gautam, Ostini, Lesa, McDonald, Cameron J., Lane, Steven W., Vu, Therese, Hooper, John D., Velasco, Gloria, Ramsay, Andrew J., Lopez-Otin, Carlos and Subramaniam, V. Nathan (2015) A critical role for murine transferrin receptor 2 in erythropoiesis during iron restriction. British Journal of Haematology, 168 6: 891-901. doi:10.1111/bjh.13225

Author Wallace, Daniel F.
Secondes, Eriza S.
Rishi, Gautam
Ostini, Lesa
McDonald, Cameron J.
Lane, Steven W.
Vu, Therese
Hooper, John D.
Velasco, Gloria
Ramsay, Andrew J.
Lopez-Otin, Carlos
Subramaniam, V. Nathan
Title A critical role for murine transferrin receptor 2 in erythropoiesis during iron restriction
Journal name British Journal of Haematology   Check publisher's open access policy
ISSN 0007-1048
Publication date 2015-03-01
Year available 2015
Sub-type Article (original research)
DOI 10.1111/bjh.13225
Volume 168
Issue 6
Start page 891
End page 901
Total pages 11
Place of publication Chichester, West Sussex, United Kingdom
Publisher Wiley-Blackwell Publishing
Collection year 2016
Language eng
Formatted abstract
Effective erythropoiesis requires an appropriate supply of iron and mechanisms regulating iron homeostasis and erythropoiesis are intrinsically linked. Iron dysregulation, typified by iron-deficiency anaemia and iron overload, is common in many clinical conditions and impacts the health of up to 30% of the world's population. The proteins transmembrane protease, serine 6 (TMPRSS6; also termed matriptase-2), HFE and transferrin receptor 2 (TFR2) play important and opposing roles in systemic iron homeostasis, by regulating expression of the iron regulatory hormone hepcidin. We have performed a systematic analysis of mice deficient in these three proteins and show that TMPRSS6 predominates over HFE and TFR2 in hepcidin regulation. The phenotype of mice lacking TMPRSS6 and TFR2 is characterized by severe anaemia and extramedullary haematopoiesis in the spleen. Stress erythropoiesis in these mice results in increased expression of the newly identified erythroid iron regulator erythroferrone, which does not appear to overcome the hepcidin overproduction mediated by loss of TMPRSS6. Extended analysis reveals that TFR2 plays an important role in erythroid cells, where it is involved in terminal erythroblast differentiation and the regulation of erythropoietin. In conclusion, we have identified an essential role for TFR2 in erythropoiesis that may provide new targets for the treatment of anaemia.
Keyword Anaemia
TMPRSS6 (matriptase 2)
Transferrin receptor 2
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Mater Research Institute-UQ (MRI-UQ)
Official 2016 Collection
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 2 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 2 times in Scopus Article | Citations
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Created: Mon, 20 Jul 2015, 15:05:16 EST by Joanne PRESTON on behalf of School of Medicine