| 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 <sup>-/-</sup> /Nme2 <sup>-/-</sup> 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. © 2009 Springer Science+Business Media, LLC. |
| Keywords: |
signal transduction; protein phosphorylation; unclassified drug; gene mutation; gene deletion; genetics; review; nonhuman; flow cytometry; protein function; mouse; phenotype; animal; metabolism; mouse mutant; mammalia; animals; mice; mice, knockout; mus; gene expression; anemia; cell maturation; erythropoiesis; protein metabolism; animal model; cell differentiation; enzymology; models, animal; animal embryo; gene expression regulation; prenatal development; gene expression regulation, developmental; transcription regulation; heterozygosity; erythroid cell; embryo, mammalian; gene control; down regulation; phosphotransferase; metabolic disorder; genetic linkage; iron transport; nucleoside diphosphate kinase; nucleoside diphosphate kinase a; nucleoside diphosphate kinase b; nm23 nucleoside diphosphate kinases; erythropoiesis development; transcriptional control; nucleotide; nme1 protein, mouse; nme2 protein, mouse; nucleoside diphosphate kinase nm23; hematocrit; nucleoside-diphosphate kinase
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