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https://hdl.handle.net/2440/124322
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Type: | Journal article |
Title: | Characterization of Tfrc-mutant mice with microcytic phenotypes |
Author: | Conway, A.J. Brown, F.C. Rank, G. Kile, B.T. Morton, C.J. Jane, S.M. Curtis, D.J. |
Citation: | Blood Advances, 2018; 2(15):1914-1922 |
Publisher: | ASH Publications |
Issue Date: | 2018 |
ISSN: | 2473-9529 2473-9537 |
Statement of Responsibility: | Ashlee J. Conway, Fiona C. Brown, Gerhard Rank, Benjamin T. Kile, Craig J. Morton, Stephen M. Jane and David J. Curtis |
Abstract: | To 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. |
Keywords: | Erythrocytes Animals Mice Mice, Mutant Strains Anemia Receptors, Transferrin Antigens, CD Point Mutation Ferritins |
Rights: | © 2018 by The American Society of Hematology |
DOI: | 10.1182/bloodadvances.2018018820 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/382900 http://purl.org/au-research/grants/nhmrc/1016647 http://purl.org/au-research/grants/nhmrc/361646 |
Published version: | http://dx.doi.org/10.1182/bloodadvances.2018018820 |
Appears in Collections: | Aurora harvest 4 Medicine publications |
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