Impaired granulopoiesis, myelodysplasia, and early lethality in CCAAT/enhancer binding protein epsilon-deficient mice.
Polymorphonuclear leukocytes are essential for host defense to infectious diseases. CCAAT/enhancer binding protein epsilon (C/EBP epsilon) is preferentially expressed in granulocytes and lymphoid cells. Mice with a null mutation in C/EBP epsilon develop normally and are fertile but fail to generate functional neutrophils and eosinophils. Opportunistic infections and tissue destruction lead to death by 3-5 months of age. 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 essential for terminal differentiation and functional maturation of committed granulocyte progenitor cells.
Yamanaka
R
R
Clinical Gene Therapy Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Barlow
C
C
Lekstrom-Himes
J
J
Castilla
L H
LH
Liu
P P
PP
Eckhaus
M
M
Decker
T
T
Wynshaw-Boris
A
A
Xanthopoulos
K G
KG
D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins; D016207:Cytokines / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005804:Genes, Lethal; D006098:Granulocytes / Q000166:cytology*; D006410:Hematopoiesis / Q000235:genetics*; D016298:Hematopoietic Cell Growth Factors / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D009190:Myelodysplastic Syndromes / Q000473:pathology*; D009687:Nuclear Proteins / Q000235:genetics*; D011995:Recombination, Genetic
D022762:CCAAT-Enhancer-Binding Proteins; D016207:Cytokines; D004268:DNA-Binding Proteins; D016298:Hematopoietic Cell Growth Factors; D009687:Nuclear Proteins