Loss of Dynamin 2 GTPase function results in microcytic anaemia

Fiona Brown, Michael Collett, Cedric S. Tremblay, Gerhard Rank, Pietro De Camilli, Carmen J. Booth, Marc Bitoun, Phillip J Robinson, Benjamin T. Kile, Stephen M. Jane, David J. Curtis

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7 Citations (Scopus)


In a dominant mouse ethylnitrosurea mutagenesis screen for genes regulating erythropoiesis, we identified a pedigree with a novel microcytic
hypochromia caused by a V235G missense mutation in Dynamin 2
(Dnm2). Mutations in Dnm2, a GTPase, are highly disease-specific and
have been implicated in four forms of human diseases: centronuclear
myopathy, Charcot-Marie Tooth neuropathy and, more recently, T-cell leukaemia and Hereditary Spastic Paraplegia, but red cell abnormalities have not been reported to date. The V235G mutation lies within a crucial GTP nucleotide-binding pocket of Dnm2, and resulted in defective GTPase activity and incompatibility with life in the homozygous state. Dnm2 is an
essential mediator of clathrin-mediated endocytosis, which is required for
the uptake of transferrin (Tf) into red cells for incorporation of haem.
Accordingly, we observed significantly reduced Tf uptake by Dnm2+/V235G cells, which led to impaired endosome formation. Despite these deficiencies, surprisingly all iron studies were unchanged, suggesting an unexplained alternative mechanism underlies microcytic anaemia in Dnm2+/V235G mice. This study provides the first in vivo evidence for the requirements of Dnm2 in normal erythropoiesis.
Original languageEnglish
Pages (from-to)616 - 628
Number of pages13
JournalBritish Journal of Haematology
Issue number4
Publication statusPublished - Sep 2017


  • microcytic anaemia
  • Dynamin 2 mutation
  • clathrin-mediated endocytosis
  • ethylnitrosurea mutagenesis
  • mouse model of anaemia

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