title: Reduced lymphocyte longevity and homeostatic proliferation in lamin B receptor-deficient mice results in profound and progressive lymphopenia.
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.
authors: Walter and Eliza Hall Institute, Parkville, Victoria 3052, Australia. anne.verhagen@csl.com.au
authors: Anne M
authors: AM
authors: Verhagen
authors: Carolyn A
authors: CA
authors: de Graaf
authors: Tracey M
authors: TM
authors: Baldwin
authors: Ankita
authors: A
authors: Goradia
authors: Janelle E
authors: JE
authors: Collinge
authors: Benjamin T
authors: BT
authors: Kile
authors: Donald
authors: D
authors: Metcalf
authors: Robyn
authors: R
authors: Starr
authors: Douglas J
authors: DJ
authors: Hilton
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D016922:Cellular Senescence / Q000235:genetics / Q000276:immunology*; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000276:immunology* / Q000473:pathology; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D017354:Point Mutation; D018160:Receptors, Cytoplasmic and Nuclear; D000097682:Lamin B Receptor
chemical_list: D018160:Receptors, Cytoplasmic and Nuclear; D000097682:Lamin B Receptor