| First Author | Postel EH | Year | 2009 |
| Journal | Dev Dyn | Volume | 238 |
| Issue | 3 | Pages | 775-87 |
| PubMed ID | 19235734 | Mgi Jnum | J:146219 |
| Mgi Id | MGI:3837057 | Doi | 10.1002/dvdy.21887 |
| Citation | Postel EH, et al. (2009) Targeted deletion of Nm23/nucleoside diphosphate kinase A and B reveals their requirement for definitive erythropoiesis in the mouse embryo. Dev Dyn 238(3):775-87 |
| abstractText | The ubiquitously expressed nucleoside diphosphate kinases (Nm23/NDPK/Awd) are a large family of multifunctional enzymes implicated in nucleic acid metabolism and in normal and abnormal development. Here, we describe the generation and characterization of NDPK A- and B-deficient (Nme1(-/-)/Nme2(-/-)) mice in which >95% of the enzyme activity is eliminated. These mice are undersized, die perinatally, and exhibit a spectrum of hematological phenotypes including severe anemia, impaired maturation of erythrocytes, and abnormal hematopoiesis in the liver and bone marrow. Flow cytometric analysis of developing Nme1(-/-)/Nme2(-/-) erythroid cells indicated that the major iron transport receptor molecule TfR1 is attenuated concomitant with a reduction of intracellular iron, suggesting that TfR1 is a downstream target of NDPKs and that reduced iron in Nme1(-/-)/Nme2(-/-) erythroblasts is inhibiting their development. We conclude that Nm23/NDPKs play critical roles in definitive erythroid development. Our novel mouse model also links erythropoiesis and nucleotide metabolism. Developmental Dynamics 238:775-787, 2009. (c) 2009 Wiley-Liss, Inc. |
