Requirement for NF-κB in osteoclast and B-cell development

被引:842
作者
Franzoso, G
Carlson, L
Xing, LP
Poljak, L
Shores, EW
Brown, KD
Leonardi, A
Tran, T
Boyce, BF
Siebenlist, U
机构
[1] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA
[2] Univ Texas, Hlth Sci Ctr, San Antonio, TX 78284 USA
[3] US FDA, Div Hematol Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA
关键词
NF-kappa B; knockout mice; osteopetrosis; B cell; development; osteoclasts;
D O I
10.1101/gad.11.24.3482
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
NF-kappa B is a family of related, dimeric transcription factors that are readily activated in cells by signals associated with stress or pathogens. These factors are critical to host defense, as demonstrated previously with mice deficient in individual subunits of NF-kappa B. We have generated mice deficient in both the p50 and p52 subunits of NF-kappa B to reveal critical functions that may be shared by these two highly homologous proteins. We now demonstrate that unlike the respective single knockout mice, the p50/p52 double knockout mice fail to generate mature osteoclasts and B cells, apparently because of defects that track with these lineages in adoptive transfer experiments. Furthermore, these mice present markedly impaired thymic and splenic architectures and impaired macrophage functions. The blocks in osteoclast and B-cell maturation were unexpected. Lack of mature osteoclasts caused severe osteopetrosis, a family of diseases characterized by impaired osteoclastic bone resorption. These findings no iv establish critical roles for NF-kappa B in development and expand its repertoire of roles in the physiology of differentiated hematopoietic cells.
引用
收藏
页码:3482 / 3496
页数:15
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