The lamin B receptor under transcriptional control of C/EBPε is required for morphological but not functional maturation of neutrophils

被引：45

作者：

Cohen, Tatiana V. ^{[1
]}

Klarmann, Kimberly D. ^{[1
,2
]}

Sakchaisri, Krisada ^{[3
]}

Cooper, Jason P. ^{[6
]}

Kuhns, Douglas ^{[4
]}

Anver, Miriam ^{[5
]}

Johnson, Peter F. ^{[3
]}

Williams, Simon C. ^{[6
]}

Keller, Jonathan R. ^{[1
,2
]}

Stewart, Colin L. ^{[1
]}

机构：

[1] CCR, Canc & Dev Biol Lab, Frederick, MD 21702 USA

[2] SAIC Frederick Inc, Lab Canc Prevent, Basic Res Program, Frederick, MD 21702 USA

[3] CCR, Lab Prot Dynam & Signaling, Frederick, MD 21702 USA

[4] SAIC Frederick Inc, Clin Serv Program, Frederick, MD 21702 USA

[5] NCI, SAIC Frederick, Pathol Histotechnol Lab, Lab Anim Sci Program, Frederick, MD 21702 USA

[6] Texas Tech Univ, Hlth Sci Ctr, Dept Biochem & Cell Biol, Lubbock, TX 79430 USA

来源：

HUMAN MOLECULAR GENETICS | 2008年 / 17卷 / 19期

基金：

美国国家卫生研究院;

关键词：

D O I：

10.1093/hmg/ddn191

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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-Huet 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 (Lbr(GT/GT)). Phenotypically, the Lbr(GT/GT) mice are similar to ichythyosis mice. The Lbr(GT/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/EBP epsilon. We identified C/EBP epsilon binding sites within the Lbr promoter and used EMSAs and luciferase assays to show that Lbr is transcriptionally regulated by C/EBP epsilon. Our findings indicate that the Lbr(GT/GT) mice are a model for Pelger-Huet anomaly and that Lbr, under transcriptional regulation of C/EBP epsilon, is necessary for morphological but not necessarily functional granulocyte maturation.

引用

页码：2921 / 2933

页数：13

共 56 条

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