IMPAIRED GRANULOPOIESIS, MYELODYSPLASIA, AND EARLY LETHALITY IN CCAATENHANCER BINDING-PROTEIN EPSILON-DEFICIENT MICE/

Polymorphonuclear leukocytes are essential for host defense to infecti ous diseases, CCAAT/enhancer binding protein epsilon (C/EBP epsilon) i s preferentially expressed in granulocytes and lymphoid cells, Mice wi th a null mutation in C/EBP epsilon develop normally and are fertile b ut fail to generate functional neutrophils and eosinophils, Opportunis tic infections and tissue destruction lead to death by 3-5 months of a ge, Furthermore, end-stage mice develop myelodysplasia, characterized by proliferation of atypical granulocytes that efface the bone marrow and result in severe tissue destruction. Thus, C/EBP epsilon is essent ial for terminal differentiation and functional maturation of committe d granulocyte progenitor cells.