Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/124984
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Type: Journal article
Title: Reduced lymphocyte longevity and homeostatic proliferation in lamin B receptor-deficient mice results in profound and progressive lymphopenia
Author: Verhagen, A.
De Graaf, C.
Baldwin, T.
Goradia, A.
Collinge, J.
Kile, B.
Metcalf, D.
Starr, R.
Hilton, D.
Citation: Journal of Immunology, 2012; 188(1):122-134
Publisher: American Association of Immunologists
Issue Date: 2012
ISSN: 0022-1767
1550-6606
Statement of
Responsibility: 
Anne M. Verhagen, Carolyn A. de Graaf, Tracey M. Baldwin, Ankita Goradia, Janelle E. Collinge, Benjamin T. Kile ... et al.
Abstract: The lamin B receptor (LBR) is a highly unusual inner nuclear membrane protein with multiple functions. Reduced levels are associated with decreased neutrophil lobularity, whereas complete absence of LBR results in severe skeletal dysplasia and in utero/perinatal lethality. We describe a mouse pedigree, Lym3, with normal bone marrow and thymic development but profound and progressive lymphopenia particularly within the T cell compartment. This defect arises from a point mutation within the Lbr gene with only trace mutant protein detectable in homozygotes, albeit sufficient for normal development. Reduced T cell homeostatic proliferative potential and life span in vivo were found to contribute to lymphopenia. To investigate the role of LBR in gene silencing in hematopoietic cells, we examined gene expression in wild-type and mutant lymph node CD8 T cells and bone marrow neutrophils. Although LBR deficiency had a very mild impact on gene expression overall, for common genes differentially expressed in both LBR-deficient CD8 T cells and neutrophils, gene upregulation prevailed, supporting a role for LBR in their suppression. In summary, this study demonstrates that LBR deficiency affects not only nuclear architecture but also proliferation, cell viability, and gene expression of hematopoietic cells.
Keywords: Lymphopenia
Rights: © 2011 by The American Association of Immunologists
RMID: 1000001795
DOI: 10.4049/jimmunol.1100942
Grant ID: http://purl.org/au-research/grants/nhmrc/461219
Appears in Collections:Medical Sciences publications

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