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

Dev Dyn. 2009 Mar;238(3):775-87. doi: 10.1002/dvdy.21887.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Anemia / genetics
  • Anemia / metabolism
  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • Cells, Cultured
  • Embryo, Mammalian / embryology*
  • Embryo, Mammalian / enzymology*
  • Erythropoiesis*
  • Gene Deletion
  • Gene Expression Regulation, Developmental
  • Globins / genetics
  • Globins / metabolism
  • Iron / blood
  • Liver / embryology
  • Liver / enzymology
  • Mice
  • NM23 Nucleoside Diphosphate Kinases / deficiency*
  • NM23 Nucleoside Diphosphate Kinases / genetics
  • NM23 Nucleoside Diphosphate Kinases / metabolism*
  • RNA, Messenger / genetics


  • Antigens, CD
  • NM23 Nucleoside Diphosphate Kinases
  • RNA, Messenger
  • Globins
  • Iron