Molecular and Cellular Biochemistry

, Volume 329, Issue 1–2, pp 45–50 | Cite as

Double knockout Nme1/Nme2 mouse model suggests a critical role for NDP kinases in erythroid development

  • Edith Horn Postel
  • Xiaoming Zou
  • Daniel A. Notterman
  • Krista M. D. La Perle
Article

Abstract

Nm23/NDP kinases A and B encoded by the Nme1/Nme2 genes are multifunctional enzymes responsible for the majority of NDP kinase activity in mammals. This review summarizes recent studies on their physiological roles using a mouse model in which both Nme1 and Nme2 genes have been deleted. The double knockout mice are stunted in growth and die perinatally. Additionally, these mice display hematologic phenotypes, including severe anemia, abnormal erythroid cell development, loss of the iron transport receptor molecule TfR1, and reduced iron uptake by Nme1 −/− /Nme2 −/− erythroid cells. We hypothesize that Nm23/NDP kinases regulate TfR1 gene expression in erythroid cells in some manner, and that defective iron transport into these cells is responsible for the anemia and death. This Nme1/Nme2 mouse model also links nucleotide metabolism with erythropoiesis, suggesting alternative or additional mechanisms that may explain the observed phenomena.

Keywords

Erythropoiesis development Transcriptional control Metabolic disorder 

Notes

Acknowledgments

This work is supported by NIH/NCI grant RO1 CA76496 (to EHP). The double heterozygous knockout mice were a gift from Amgen Inc. The authors acknowledge helpful discussions with Drs. Achille Iolascon and Stefano Rivella.

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Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Edith Horn Postel
    • 1
  • Xiaoming Zou
    • 2
  • Daniel A. Notterman
    • 3
  • Krista M. D. La Perle
    • 4
    • 5
  1. 1.Laboratory of Biochemistry and Molecular Biology, Department of PediatricsRobert Wood Johnson Medical School/UMDNJNew BrunswickUSA
  2. 2.AMGEN Inc.Thousand OaksUSA
  3. 3.Department of Molecular BiologyPrinceton UniversityPrincetonUSA
  4. 4.Genetically Engineered Mouse Phenotyping ServiceMemorial Sloan-Kettering Cancer CenterNew YorkUSA
  5. 5.Department of Veterinary Biosciences, Comparative Pathology Program & Mouse Phenotyping Shared ResourceThe Ohio State UniversityColumbusUSA

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