Neutrophil-specific granule deficiency results from a novel mutation with loss of function of the transcription factor CCAAT/enhancer binding protein ε

Julie A. Lekstrom-Himes, Susan E. Dorman, Piroska Kopar, Steven M. Holland, John I. Gallin

Research output: Contribution to journalArticle

Abstract

Neutrophil-specific granule deficiency (SGD) is a rare disorder characterized by recurrent pyogenic infections, defective neutrophil chemotaxis and bactericidal activity, and lack of neutrophil secondary granule proteins. CCAAT/enhancer binding protein (C/EBP)ε, a member of the leucine zipper family of transcription factors, is expressed primarily in myeloid cells, and its knockout mouse model possesses distinctive defects, including a lack of neutrophil secondary granule proteins. Sequence analysis of the genomic DNA of a patient with SGD revealed a five-basepair deletion in the second exon of the C/EBPε locus. The predicted frame shift results in a truncation of the 32-kD major C/EBPε isoform, with loss of the dimerization domain, DNA binding region, and transcriptional activity. The multiple functional defects observed in these early neutrophil progenitor cells, a consequence of C/EBPε deficiency, define SGD as a defect in myelopoiesis and establish the requirement for C/EBPε for the promyelocyte-myelocyte transition in myeloid differentiation.

Original languageEnglish (US)
Pages (from-to)1847-1852
Number of pages6
JournalJournal of Experimental Medicine
Volume189
Issue number11
DOIs
StatePublished - Jun 7 1999

Keywords

  • Granulocyte
  • Immunodeficiency
  • Lactoferrin
  • Myelopoiesis
  • Neutrophil

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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