Characterization of Tfrc-mutant mice with microcytic phenotypes

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dc.contributor.authorConway, A.J.
dc.contributor.authorBrown, F.C.
dc.contributor.authorRank, G.
dc.contributor.authorKile, B.T.
dc.contributor.authorMorton, C.J.
dc.contributor.authorJane, S.M.
dc.contributor.authorCurtis, D.J.
dc.date.issued2018
dc.description.abstractTo identify novel regulators of erythropoiesis, we performed independent forward genetic screens using the chemical mutagen ENU in mice. Among progeny displaying microcytic red-cell phenotypes, 7 independent mouse strains harboring mutations within the transferrin receptor gene Tfrc were identified. Six of the mutants, including the previously described red blood cell 6 (RBC6) strain, displayed reduced erythroblast CD71 expression and midgestation lethality of homozygotes (E12.5-E14.5), and 1 novel strain, RBC21, displayed a variable phenotype with sustained CD71 expression and late homozygous lethality (E18.5). Standard iron studies were normal in the RBC21 mutant, but intracellular ferritin was significantly reduced. The microcytic phenotype seen in the RBC21 strain was the result of impaired binding of transferrin to the receptor. Neither RBC6 nor RBC21 responded to iron replacement therapy. These studies describe how point mutations of the transferrin receptor can cause a microcytic anemia that does not respond to iron therapy and would not be detected by routine iron studies, such as serum ferritin.
dc.description.statementofresponsibilityAshlee J. Conway, Fiona C. Brown, Gerhard Rank, Benjamin T. Kile, Craig J. Morton, Stephen M. Jane and David J. Curtis
dc.identifier.citationBlood advances, 2018; 2(15):1914-1922
dc.identifier.doi10.1182/bloodadvances.2018018820
dc.identifier.issn2473-9529
dc.identifier.issn2473-9537
dc.identifier.orcidKile, B.T. [0000-0002-8836-8947]
dc.identifier.urihttp://hdl.handle.net/2440/124322
dc.language.isoen
dc.publisherASH Publications
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/382900
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1016647
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/361646
dc.rights© 2018 by The American Society of Hematology
dc.source.urihttps://doi.org/10.1182/bloodadvances.2018018820
dc.subjectErythrocytes
dc.subjectAnimals
dc.subjectMice
dc.subjectMice, Mutant Strains
dc.subjectAnemia
dc.subjectReceptors, Transferrin
dc.subjectAntigens, CD
dc.subjectPoint Mutation
dc.subjectFerritins
dc.titleCharacterization of Tfrc-mutant mice with microcytic phenotypes
dc.typeJournal article
pubs.publication-statusPublished

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