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- Title
The lamin B receptor under transcriptional control of C/EBPɛ is required for morphological but not functional maturation of neutrophils.
- Authors
Cohen, Tatiana V.; Klarmann, Kimberly D.; Sakchaisri, Krisada; Cooper, Jason P.; Kuhns, Douglas; Anver, Miriam; Johnson, Peter F.; Williams, Simon C.; Keller, Jonathan R.; Stewart, Colin L.
- Abstract
The lamin B receptor (LBR) is an integral nuclear envelope protein that interacts with chromatin and has homology to sterol reductases. Mutations in LBR result in Pelger–Huët anomaly and HEM–Greenberg skeletal dysplasia, whereas in mice Lbr mutations result in ichthyosis. To further understand the function of the LBR and its role in disease, we derived a novel mouse model with a gene-trap insertion into the Lbr locus (LbrGT/GT). Phenotypically, the LbrGT/GT mice are similar to ichthyosis mice. The LbrGT/GT granulocytes lack a mature segmented nucleus and have a block in late maturation. Despite these changes in nuclear morphology, the innate granulocyte immune function in the killing of Staphylococcus aureus bacteria appears to be intact. Granulocyte differentiation requires the transcription factor C/EBPɛ. We identified C/EBPɛ binding sites within the Lbr promoter and used EMSAs and luciferase assays to show that Lbr is transcriptionally regulated by C/EBPɛ. Our findings indicate that the LbrGT/GT mice are a model for Pelger–Huët anomaly and that Lbr, under transcriptional regulation of C/EBPɛ, is necessary for morphological but not necessarily functional granulocyte maturation.
- Publication
Human Molecular Genetics, 2008, Vol 17, Issue 19, p2921
- ISSN
0964-6906
- Publication type
Article
- DOI
10.1093/hmg/ddn191