TY - JOUR
T1 - Double knockout Nme1/Nme2 mouse model suggests a critical role for NDP kinases in erythroid development
AU - Postel, Edith Horn
AU - Zou, Xiaoming
AU - Notterman, Daniel A.
AU - La Perle, Krista M.D.
N1 - Funding Information:
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.
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
KW - Erythropoiesis development
KW - Metabolic disorder
KW - Transcriptional control
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U2 - 10.1007/s11010-009-0110-9
DO - 10.1007/s11010-009-0110-9
M3 - Article
C2 - 19381783
AN - SCOPUS:70449719474
SN - 0300-8177
VL - 329
SP - 45
EP - 50
JO - Molecular and Cellular Biochemistry
JF - Molecular and Cellular Biochemistry
IS - 1-2
ER -