| First Author | Brown FC | Year | 2017 |
| Journal | Br J Haematol | Volume | 178 |
| Issue | 4 | Pages | 616-628 |
| PubMed ID | 28466468 | Mgi Jnum | J:330452 |
| Mgi Id | MGI:6883120 | Doi | 10.1111/bjh.14709 |
| Citation | Brown FC, et al. (2017) Loss of Dynamin 2 GTPase function results in microcytic anaemia. Br J Haematol 178(4):616-628 |
| abstractText | 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. |
