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- Title
Targeted deletion of Nm23/nucleoside diphosphate kinase A and B reveals their requirement for definitive erythropoiesis in the mouse embryo.
- Authors
Postel, Edith H.; Wohlman, Irene; Zou, Xiaoming; Juan, Todd; Sun, Ning; D'Agostin, Diane; Cuellar, Maria; Choi, Theresa; Notterman, Daniel A.; La Perle, Krista M.D.
- Abstract
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.
- Publication
Developmental Dynamics, 2009, Vol 238, Issue 3, p775
- ISSN
1058-8388
- Publication type
Article
- DOI
10.1002/dvdy.21887