title: Human α-defensin expression is not dependent on CCAAT/enhancer binding protein-ε in a murine model.
abstract: Specific granule deficiency (SGD) is a rare congenital disorder characterized by recurrent infections. The disease is caused by inactivating mutations of the CCAAT/enhancer binding protein-ε (C/EBP-ε) gene. As a consequence, specific and gelatinase granules lack most matrix proteins. Furthermore, azurophil granules contain diminished amounts of their most abundant proteins, α-defensins, also known as human neutrophil peptides (HNPs). In accordance with this, in vitro models have demonstrated induction of HNPs by C/EBP-ε. Since mice do not express myeloid defensins, they cannot per se be used to characterize the role of C/EBP-ε in controlling HNP expression in vivo. We therefore crossed a transgenic HNP-1-expressing mouse with the Cebpe-/- mouse to study the in vivo significance of C/EBP-ε for HNP-1 transcription and expression. Surprisingly, neither expression nor processing of HNP-1 was affected by lack of C/EBP-ε in these mice. Transduction of C/EBP-ε into primary bone marrow cells from HNP-1 mice induced some HNP-1 expression, but not to levels comparable to expression human cells. Taken together, our data infer that the HNP-1 of the transgenic mouse does not show an expression pattern equivalent to endogenous secondary granule proteins. This limits the use of these transgenic mice as a model for human conditions.
authors.affiliation: The Granulocyte Research Laboratory, Department of Hematology, National University Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Andreas
authors.initials: A
authors.lastname: Glenthøj
authors.affiliation: The Granulocyte Research Laboratory, Department of Hematology, National University Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Sara
authors.initials: S
authors.lastname: Dahl
authors.affiliation: The Granulocyte Research Laboratory, Department of Hematology, National University Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Maria T
authors.initials: MT
authors.lastname: Larsen
authors.affiliation: The Granulocyte Research Laboratory, Department of Hematology, National University Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jack B
authors.initials: JB
authors.lastname: Cowland
authors.affiliation: The Granulocyte Research Laboratory, Department of Hematology, National University Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Borregaard
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D022762:CCAAT-Enhancer-Binding Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D023421:Models, Animal; D011401:Promoter Regions, Genetic / Q000502:physiology; D014161:Transduction, Genetic; D023084:alpha-Defensins / Q000096:biosynthesis* / Q000378:metabolism
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C489468:Cebpe protein, mouse; D023084:alpha-Defensins; C406413:human neutrophil peptide 1; C070790:CEBPE protein, human