Double knockout Nme1/Nme2 mouse model suggests a critical role for NDP kinases in erythroid development.
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.
Postel
Edith Horn
EH
Laboratory of Biochemistry and Molecular Biology, Department of Pediatrics, Robert Wood Johnson Medical School/UMDNJ, New Brunswick, NJ, USA. posteleh@umdnj.edu
Zou
Xiaoming
X
Notterman
Daniel A
DA
La Perle
Krista M D
KM
D000818:Animals; D004622:Embryo, Mammalian / Q000196:embryology / Q000201:enzymology; D004920:Erythropoiesis; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D054778:NM23 Nucleoside Diphosphate Kinases / Q000235:genetics*; D009701:Nucleoside-Diphosphate Kinase / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*
D054778:NM23 Nucleoside Diphosphate Kinases; C517939:Nme1 protein, mouse; C517941:Nme2 protein, mouse; D009701:Nucleoside-Diphosphate Kinase