Targeted deletion of Nm23/nucleoside diphosphate kinase A and B reveals their requirement for definitive erythropoiesis in the mouse embryo.

Published on Mar 1, 2009in Developmental Dynamics3.275
· DOI :10.1002/DVDY.21887
Edith H. Postel6
Estimated H-index: 6
(RU: Rutgers University),
Irene M. Wohlman3
Estimated H-index: 3
(RU: Rutgers University)
+ 7 AuthorsKrista M.D. La Perle6
Estimated H-index: 6
(MSK: Memorial Sloan Kettering Cancer Center)
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. © 2009 Wiley-Liss, Inc.
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