Naslov
Requirement for NF-kB in osteoclast and B-cell development
(Requirement for NF-kB in osteoclast and B cell development)

Autori
Fransozo, Guido ; Carlson, Louise ; Xing, Lianping ; Poljak, Ljiljana ; Leonardi, Antonio ; Tran, Tom ; Boyce Brendan F ; Shores, W. Elizabeth ; Brown, D. Keith ; Siebenlist, Ulrich

Izvornik
Genes and Development (0890-9369) 11 (1997); 3482-3496

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
NF-kB transcription factor; B cell development; osteoclast development; osteopetrosis

Sažetak
NF-κ 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-κ B. We have generated mice deficient in both the p50 and p52 subunits of NF-κ 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 now establish critical roles for NF-κ B in development and expand its repertoire of roles in the physiology of differentiated hematopoietic cells.

Izvorni jezik
Engleski

POVEZANOST RADA