Targeted deletion of Nm23/Nucleoside Diphosphate Kinase A and B reveals their requirement for definitive erythropoiesis in the mouse embryo

Edith H. Postel, Irene Wohlman, Xiaoming Zou, Todd Juan, Ning Sun, Diane D'Agostin, Maria Cuellar, Theresa Choi, Daniel A. Notterman, Krista M.D. La Perle

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31 Scopus citations

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 (Nme 1-/-/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.

Original languageEnglish (US)
Pages (from-to)775-787
Number of pages13
JournalDevelopmental Dynamics
Volume238
Issue number3
DOIs
StatePublished - Mar 1 2009

All Science Journal Classification (ASJC) codes

  • Developmental Biology

Keywords

  • Anemia
  • Erythropoiesis
  • Iron transport
  • NDP kinase
  • Nm23
  • Transcriptional regulation

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    Postel, E. H., Wohlman, I., Zou, X., Juan, T., Sun, N., D'Agostin, D., Cuellar, M., Choi, T., Notterman, D. A., & La Perle, K. M. D. (2009). Targeted deletion of Nm23/Nucleoside Diphosphate Kinase A and B reveals their requirement for definitive erythropoiesis in the mouse embryo. Developmental Dynamics, 238(3), 775-787. https://doi.org/10.1002/dvdy.21887