Reduced oxidative-stress response in red blood cells from p45NFE2-deficient mice

p45NF-E2 is a member of the cap 'n' collar (CNC)-basic leucine zipper famil y of transcriptional activators that is expressed at high levels in various types of blood cells. Mice deficient in p45NF-E2 that were generated by ge ne targeting have high mortality from bleeding resulting from severe thromb ocytopenia. Surviving p45nf-e2(-/-) adults have mild anemia characterized b y hypochromic red blood cells (RBCs), reticulocytosis, and splenomegaly. Er ythroid abnormalities in p45nf-e2(-/-) animals were previously attributed t o stress erythropoiesis caused by chronic bleeding and, possibly, ineffecti ve erythropoiesis. Previous studies suggested that CNC factors might play e ssential roles in regulating expression of genes that protect cells against oxidative stress. In this study, we found that p45NF-E2-deficient RBCs hav e increased levels of reactive oxygen species and an increased susceptibili ty to oxidative-stress-induced damage. Deformability of p45NF-E2-deficient RBCs was markedly reduced with oxidative stress, and mutant cells had a red uced life span. One possible reason for increased sensitivity to oxidative stress is that catalase levels were reduced in mutant RBCs. These findings suggest a role for p45NF-E2 in the oxidative-stress response in RBCs and in dicate that p45NF-E2 deficiency contributes to the anemia in p45nf-e2(-/-) mice. (Blood, 2001;97:2151-2158) (C) 2001 by The American Society of Hemato logy.