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Targeted deletion of Nm23/nucleoside diphosphate kinase A and B reveals their requirement for definitive erythropoiesis in the mouse embryo
Author(s) -
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.
Publication year - 2009
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.21887
Subject(s) - erythropoiesis , biology , nucleoside diphosphate kinase , haematopoiesis , ineffective erythropoiesis , kinase , nucleoside triphosphate , intracellular , embryo , bone marrow , microbiology and biotechnology , gene , nucleotide , biochemistry , anemia , immunology , medicine , stem cell
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.