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

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

doi:10.1101/gad.11.24.3482

Cited by 996NF-κB Signaling PathwaysBone Metabolism and DiseasesT-cell and B-cell Immunology

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

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Franzoso, Guido, Carlson, Louise, Xing, Lianping, Poljak, Ljiljana, Shores, Elizabeth W., Brown, Keith D., Leonardi, Antonio, Tran, Tom +2 more·1997·Genes & Development

DOI 10.1101/gad.11.24.3482PMC PMC316809

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Abstract

NF-κB 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-κB. We have generated mice deficient in both the p50 and p52 subunits of NF-κB 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-κB in development and expand its repertoire of roles in the physiology of differentiated hematopoietic cells.

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Mice lacking both NF-κB 1 and 2 display severe osteopetrosis due to accumulation of osteoclast precursors.
“Mice lacking both NF-κB 1 and 2 display, among other features, severe osteopetrosis165 due to an accumulation of osteoclast precursors.166”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [165]

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Research works printed but not linked: 1

Franzoso, G., L. Carlson, L. Poljak, E.W. Shores, S. Epstein, A. Leonardi, A. Grinberg, T. Tran, T. Scharton-Kersten, M. An- ver, P. Love, K. Brown, and U. Siebenlist. 1998. Mice defi- cient in NF-B/p52 present with deficits in humoral re- sponses, germinal center reactions and splenic microarchi- tecture. J. Exp. Med. (in press).

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A novel X-linked disorder of immune deficiency and hypohidrotic ectodermal dysplasia is allelic to incontinentia pigmenti and due to mutations in IKK-gamma (NEMO)
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Authors: Franzoso, G., Carlson, L., Xing, L., Poljak, L., Shores, E. W., Brown, K. D., Leonardi, A., Tran, T., Boyce, B. F., & Siebenlist, U.
Affiliations: National Institutes of Health (US)
ORCID: Franzoso, Guido
Xing, Lianping
Poljak, Ljiljana
Leonardi, Antonio
Boyce, Brendan F.
Siebenlist, Ulrich
Venue: Genes & Development
Publisher: Cold Spring Harbor Laboratory
Published: 1997-12-15
Volume: 11
Issue: 24
Pages: 3482-3496
ISSN: 0890-9369 (ISSN-L)
1549-5477
DOI: 10.1101/gad.11.24.3482
PMC: PMC316809
OpenAlex: W2049293744
Cited by: 996
References: 86
Citations by year: 2026: 9 · 2025: 7 · 2024: 17 · 2023: 17 · 2022: 16 · 2021: 31 · 2020: 29 · 2019: 27 · 2018: 29 · 2017: 28 · 2016: 28 · 2015: 50 · 2014: 37 · 2013: 34 · 2012: 46
Type: posted content
Language: en
Open access: bronze
doi.org
Locations: Genes & Development (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
HighWire Press Open Archive (submittedVersion)
Funders: National Institutes of Health
National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR 43510, R01AR043510)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords: NF-κB, p50 subunit, double knockout mice, osteoclastogenesis, B cell development, osteopetrosis, bone resorption, thymic architecture, splenic architecture, macrophage function, hematopoietic differentiation, transcription factors
MeSH terms: Animals, B-Lymphocytes, Macrophages, Mice, Inbred Strains, Mice, Mutant Strains, Osteoclasts, Osteopetrosis, Spleen, Thymus Gland, NF-kappa B, Mice, Knockout, Mice, NF-kappa B p50 Subunit

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

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