{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T06:17:20Z","timestamp":1789885040224,"version":"4.0.1"},"reference-count":39,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,11,17]],"date-time":"2014-11-17T00:00:00Z","timestamp":1416182400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1048000"],"award-info":[{"award-number":["APP1048000"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2015,3]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Effective erythropoiesis requires an appropriate supply of iron and mechanisms regulating iron homeostasis and erythropoiesis are intrinsically linked. Iron dysregulation, typified by iron\u2010deficiency 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 (<jats:styled-content style=\"fixed-case\">TMPRSS<\/jats:styled-content>6; also termed matriptase\u20102), <jats:styled-content style=\"fixed-case\">HFE<\/jats:styled-content> and transferrin receptor 2 (<jats:styled-content style=\"fixed-case\">TFR<\/jats:styled-content>2) 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 <jats:styled-content style=\"fixed-case\">TMPRSS<\/jats:styled-content>6 predominates over <jats:styled-content style=\"fixed-case\">HFE<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">TFR<\/jats:styled-content>2 in hepcidin regulation. The phenotype of mice lacking <jats:styled-content style=\"fixed-case\">TMPRSS<\/jats:styled-content>6 and <jats:styled-content style=\"fixed-case\">TFR<\/jats:styled-content>2 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 <jats:styled-content style=\"fixed-case\">TMPRSS<\/jats:styled-content>6. Extended analysis reveals that <jats:styled-content style=\"fixed-case\">TFR<\/jats:styled-content>2 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 <jats:styled-content style=\"fixed-case\">TFR<\/jats:styled-content>2 in erythropoiesis that may provide new targets for the treatment of anaemia.<\/jats:p>","DOI":"10.1111\/bjh.13225","type":"journal-article","created":{"date-parts":[[2014,11,18]],"date-time":"2014-11-18T04:32:07Z","timestamp":1416285127000},"page":"891-901","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["A critical role for murine transferrin receptor 2 in erythropoiesis during iron restriction"],"prefix":"10.1111","volume":"168","author":[{"given":"Daniel F.","family":"Wallace","sequence":"first","affiliation":[{"name":"Membrane Transport Laboratory QIMR Berghofer Medical Research Institute Brisbane Qld Australia"},{"name":"School of Medicine The University of Queensland Brisbane Qld Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eriza S.","family":"Secondes","sequence":"additional","affiliation":[{"name":"Membrane Transport Laboratory QIMR Berghofer Medical Research Institute Brisbane Qld Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gautam","family":"Rishi","sequence":"additional","affiliation":[{"name":"Membrane Transport Laboratory QIMR Berghofer Medical Research Institute Brisbane Qld Australia"},{"name":"School of Medicine The University of Queensland Brisbane Qld Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lesa","family":"Ostini","sequence":"additional","affiliation":[{"name":"Membrane Transport Laboratory QIMR Berghofer Medical Research Institute Brisbane Qld Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cameron J.","family":"McDonald","sequence":"additional","affiliation":[{"name":"Membrane Transport Laboratory QIMR Berghofer Medical Research Institute Brisbane Qld Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven W.","family":"Lane","sequence":"additional","affiliation":[{"name":"School of Medicine The University of Queensland Brisbane Qld Australia"},{"name":"Translational Leukaemia Research Laboratory QIMR Berghofer Medical Research Institute Brisbane Qld Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Therese","family":"Vu","sequence":"additional","affiliation":[{"name":"School of Medicine The University of Queensland Brisbane Qld Australia"},{"name":"Translational Leukaemia Research Laboratory QIMR Berghofer Medical Research Institute Brisbane Qld Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D.","family":"Hooper","sequence":"additional","affiliation":[{"name":"Translational Research Institute Mater Research Institute\u2010University of Queensland Brisbane Qld Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Velasco","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular Instituto Universitario de Oncolog\u00eda Universidad de Oviedo Oviedo Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Ramsay","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular Instituto Universitario de Oncolog\u00eda Universidad de Oviedo Oviedo Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Lopez\u2010Otin","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular Instituto Universitario de Oncolog\u00eda Universidad de Oviedo Oviedo Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V. Nathan","family":"Subramaniam","sequence":"additional","affiliation":[{"name":"Membrane Transport Laboratory QIMR Berghofer Medical Research Institute Brisbane Qld Australia"},{"name":"School of Medicine The University of Queensland Brisbane Qld Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,11,17]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.335"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1777"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)12602-5"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20122760"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI44883"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0909296106"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1462399410001687"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1157121"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.130"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-10-315507"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.051630898"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-04-149773"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-04-281360"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminhematol.2009.06.001"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI66969"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2010.195057"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-03-143354"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2996"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V98.9.2714"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0145-2126(03)00100-0"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcmd.2011.12.005"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009594"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.320"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2013.103143"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1104742"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-08-3042"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0215686"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-09-307462"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp315"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-09-453977"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2008.09.012"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1629"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-12-195503"},{"key":"e_1_2_8_35_1","first-page":"9","article-title":"A simple technique for measuring storage iron concentrations in formalinised liver samples","volume":"33","author":"Torrance J.D.","year":"1968","journal-title":"The South African Journal of Medical Sciences"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2009.07873.x"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2004.062018"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2006.11.028"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23198"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng2059"}],"container-title":["British Journal of Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbjh.13225","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bjh.13225","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T15:34:07Z","timestamp":1696347247000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bjh.13225"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,11,17]]},"references-count":39,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2015,3]]}},"alternative-id":["10.1111\/bjh.13225"],"URL":"https:\/\/doi.org\/10.1111\/bjh.13225","archive":["Portico"],"relation":{},"ISSN":["0007-1048","1365-2141"],"issn-type":[{"value":"0007-1048","type":"print"},{"value":"1365-2141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,11,17]]},"assertion":[{"value":"2014-07-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-09-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-11-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}