Human α-Defensin Expression Is Not Dependent on CCAAT/Enhancer Binding Protein-ε in a Murine Model
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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.
Original language | English |
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Article number | e92471 |
Journal | PLOS ONE |
Volume | 9 |
Issue number | 3 |
Pages (from-to) | 1-8 |
Number of pages | 8 |
ISSN | 1932-6203 |
DOIs | |
Publication status | Published - 2014 |
- Animals, Bone Marrow Cells, CCAAT-Enhancer-Binding Proteins, Humans, Mice, Inbred C57BL, Mice, Transgenic, Models, Animal, Promoter Regions, Genetic, Transduction, Genetic, alpha-Defensins
Research areas
ID: 138732886