PMID- 30093529
OWN - NLM
STAT- MEDLINE
DCOM- 20190403
LR  - 20190403
IS  - 2473-9537 (Electronic)
IS  - 2473-9529 (Print)
IS  - 2473-9529 (Linking)
VI  - 2
IP  - 15
DP  - 2018 Aug 14
TI  - Characterization of Tfrc-mutant mice with microcytic phenotypes.
PG  - 1914-1922
LID - 10.1182/bloodadvances.2018018820 [doi]
AB  - 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.
CI  - (c) 2018 by The American Society of Hematology.
FAU - Conway, Ashlee J
AU  - Conway AJ
AUID- ORCID: 0000-0002-9000-7366
AD  - Australian Centre for Blood Diseases, Central Clinical School, Monash University, 
      Melbourne, Australia.
FAU - Brown, Fiona C
AU  - Brown FC
AUID- ORCID: 0000-0001-9711-9769
AD  - Australian Centre for Blood Diseases, Central Clinical School, Monash University, 
      Melbourne, Australia.
FAU - Rank, Gerhard
AU  - Rank G
AD  - Rotary Bone Marrow Research Laboratory, Royal Melbourne Hospital, Melbourne, 
      Australia.
FAU - Kile, Benjamin T
AU  - Kile BT
AUID- ORCID: 0000-0002-8836-8947
AD  - The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
AD  - Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash 
      University, Melbourne, Australia.
FAU - Morton, Craig J
AU  - Morton CJ
AUID- ORCID: 0000-0001-5452-5193
AD  - Australian Cancer Research Foundation Rational Drug Discovery Centre, St. 
      Vincent's Institute of Medical Research, Fitzroy, Australia.
FAU - Jane, Stephen M
AU  - Jane SM
AUID- ORCID: 0000-0002-1045-0481
AD  - The Alfred Hospital, Melbourne, Australia; and.
FAU - Curtis, David J
AU  - Curtis DJ
AUID- ORCID: 0000-0001-9497-0996
AD  - Australian Centre for Blood Diseases, Central Clinical School, Monash University, 
      Melbourne, Australia.
AD  - Department of Clinical Haematology, Central Clinical School, Monash University, 
      Melbourne, Australia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood Adv
JT  - Blood advances
JID - 101698425
RN  - 0 (Antigens, CD)
RN  - 0 (CD71 antigen)
RN  - 0 (Receptors, Transferrin)
RN  - 0 (Tfrc protein, mouse)
RN  - 9007-73-2 (Ferritins)
SB  - IM
MH  - *Anemia/blood/genetics/pathology
MH  - Animals
MH  - Antigens, CD/*biosynthesis/genetics
MH  - Erythrocytes/*metabolism/pathology
MH  - Ferritins/*blood
MH  - Mice
MH  - Mice, Mutant Strains
MH  - *Point Mutation
MH  - Receptors, Transferrin/*biosynthesis/*genetics/metabolism
PMC - PMC6093728
COIS- Conflict-of-interest disclosure: The authors declare no competing financial 
      interests.
EDAT- 2018/08/11 06:00
MHDA- 2019/04/04 06:00
PMCR- 2018/08/09
CRDT- 2018/08/11 06:00
PHST- 2018/03/23 00:00 [received]
PHST- 2018/06/15 00:00 [accepted]
PHST- 2018/08/11 06:00 [entrez]
PHST- 2018/08/11 06:00 [pubmed]
PHST- 2019/04/04 06:00 [medline]
PHST- 2018/08/09 00:00 [pmc-release]
AID - bloodadvances.2018018820 [pii]
AID - 2018/018820 [pii]
AID - 10.1182/bloodadvances.2018018820 [doi]
PST - ppublish
SO  - Blood Adv. 2018 Aug 14;2(15):1914-1922. doi: 10.1182/bloodadvances.2018018820.