{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:15:58Z","timestamp":1791353758292,"version":"4.3.1"},"reference-count":83,"publisher":"Cold Spring Harbor Laboratory","issue":"24","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Dev."],"published-print":{"date-parts":[[1997,12,15]]},"abstract":"<jats:p>NF-\u03baB 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-\u03baB. We have generated mice deficient in both the p50 and p52 subunits of NF-\u03baB 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-\u03baB in development and expand its repertoire of roles in the physiology of differentiated hematopoietic cells.<\/jats:p>","DOI":"10.1101\/gad.11.24.3482","type":"journal-article","created":{"date-parts":[[2008,2,20]],"date-time":"2008-02-20T22:15:26Z","timestamp":1203545726000},"page":"3482-3496","source":"Crossref","is-referenced-by-count":869,"title":["Requirement for NF-\u03baB in osteoclast and B-cell\u2009development"],"prefix":"10.1101","volume":"11","author":[{"given":"Guido","family":"Franzoso","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Carlson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianping","family":"Xing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ljiljana","family":"Poljak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth W.","family":"Shores","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith D.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Leonardi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Tran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendan F.","family":"Boyce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Siebenlist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"246","published-online":{"date-parts":[[1997,12,15]]},"reference":[{"key":"2021111418500509000_11.24.3482.1","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1002\/jlb.52.1.34","article-title":"Two populations of splenic dendritic cells detected with M342, a new monoclonal antibody to an intracellular antigen of interdigitating dendritic cells and some B lymphocytes.","volume":"52","author":"Agger","year":"1992","journal-title":"J. Leukocyte Biol."},{"key":"2021111418500509000_11.24.3482.2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.14.1.73"},{"key":"2021111418500509000_11.24.3482.3","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.12.040194.001041"},{"key":"2021111418500509000_11.24.3482.4","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.14.1.649"},{"key":"2021111418500509000_11.24.3482.5","doi-asserted-by":"publisher","DOI":"10.1126\/science.274.5288.782"},{"key":"2021111418500509000_11.24.3482.6","doi-asserted-by":"publisher","DOI":"10.1101\/gad.9.22.2736"},{"key":"2021111418500509000_11.24.3482.7","doi-asserted-by":"publisher","DOI":"10.1038\/376167a0"},{"key":"2021111418500509000_11.24.3482.8","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.12.1.393"},{"key":"2021111418500509000_11.24.3482.9","doi-asserted-by":"publisher","DOI":"10.1084\/jem.185.11.1897"},{"key":"2021111418500509000_11.24.3482.10","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90401-B"},{"key":"2021111418500509000_11.24.3482.11","doi-asserted-by":"crossref","first-page":"1622","DOI":"10.1172\/JCI116032","article-title":"Requirement of pp60c-scr expression for osteoclasts to form ruffled borders and resorb bone in mice.","volume":"90","author":"Boyce","year":"1992","journal-title":"J. Clin. Invest."},{"key":"2021111418500509000_11.24.3482.12","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830171105"},{"key":"2021111418500509000_11.24.3482.13","doi-asserted-by":"publisher","DOI":"10.1038\/373531a0"},{"key":"2021111418500509000_11.24.3482.14","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1242\/dev.118.4.1221","article-title":"Expression of relB transcripts during lymphoid organ development: Specific expression in dendritic antigen-presenting cells.","volume":"118","author":"Carrasco","year":"1993","journal-title":"Development"},{"key":"2021111418500509000_11.24.3482.15","doi-asserted-by":"crossref","first-page":"2991","DOI":"10.1242\/dev.120.10.2991","article-title":"Developmental expression of the mouse c-rel proto-oncogene in hematopoietic organs.","volume":"120","author":"Carrasco","year":"1994","journal-title":"Development"},{"key":"2021111418500509000_11.24.3482.16","doi-asserted-by":"crossref","first-page":"2558","DOI":"10.4049\/jimmunol.158.6.2558","article-title":"Thymic cortical epithelium is sufficient for the development of mature T cells in relB-deficient mice.","volume":"158","author":"DeKoning","year":"1997","journal-title":"J. Immunol."},{"key":"2021111418500509000_11.24.3482.17","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/11.5.1475"},{"key":"2021111418500509000_11.24.3482.18","doi-asserted-by":"publisher","DOI":"10.1084\/jem.185.5.953"},{"key":"2021111418500509000_11.24.3482.19","first-page":"2","article-title":"B-cell development and differentiation.","volume":"34","author":"Duchosal","year":"1997","journal-title":"Semin. Hematol."},{"key":"2021111418500509000_11.24.3482.20","doi-asserted-by":"crossref","first-page":"2971","DOI":"10.4049\/jimmunol.134.5.2971","article-title":"Epithelial heterogeneity in the murine thymus: Fucose-specific lectins bind medullary epithelial cells.","volume":"134","author":"Farr","year":"1985","journal-title":"J. Immunol."},{"key":"2021111418500509000_11.24.3482.21","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1002\/jbmr.5650050716","article-title":"Impairment of macrophage colony-stimulating factor production and lack of resident bone marrow macrophages in the osteopetrotic op\/op mouse.","volume":"5","author":"Felix","year":"1990","journal-title":"J. Bone Miner. Res."},{"key":"2021111418500509000_11.24.3482.22","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830261102"},{"key":"2021111418500509000_11.24.3482.23","doi-asserted-by":"publisher","DOI":"10.1038\/359339a0"},{"key":"2021111418500509000_11.24.3482.24","doi-asserted-by":"crossref","first-page":"3893","DOI":"10.1002\/j.1460-2075.1993.tb06067.x","article-title":"The oncoprotein Bcl-3 can facilitate NF-\u03baB-mediated transactivation by removing inhibiting p50 homodimers from select \u03baB sites.","volume":"12","author":"Franzoso","year":"1993","journal-title":"EMBO J."},{"key":"2021111418500509000_11.24.3482.25","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80291-5"},{"key":"2021111418500509000_11.24.3482.26","doi-asserted-by":"crossref","unstructured":"Franzoso, G., L. Carlson, L. Poljak, E.W. Shores, S. Epstein, A. Leonardi, A. Grinberg, T. Tran, T. Scharton-Kersten, M. Anver, P. Love, K. Brown, and U. Siebenlist. 1998. Mice deficient in NF-\u03baB\/p52 present with deficits in humoral responses, germinal center reactions and splenic microarchitecture. J. Exp. Med. (in press)..","DOI":"10.1084\/jem.187.2.147"},{"key":"2021111418500509000_11.24.3482.27","doi-asserted-by":"publisher","DOI":"10.1101\/gad.7.7b.1354"},{"key":"2021111418500509000_11.24.3482.28","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.8.3405"},{"key":"2021111418500509000_11.24.3482.29","doi-asserted-by":"publisher","DOI":"10.1126\/science.7939685"},{"key":"2021111418500509000_11.24.3482.30","doi-asserted-by":"crossref","first-page":"7099","DOI":"10.1002\/j.1460-2075.1996.tb01101.x","article-title":"The Rel subunit of NF-\u03baB-like transcription factors is a positive and negative regulator of macrophage gene expression: Distinct roles for Rel in different macrophage populations.","volume":"15","author":"Grigoriadis","year":"1996","journal-title":"EMBO J."},{"key":"2021111418500509000_11.24.3482.31","doi-asserted-by":"publisher","DOI":"10.1126\/science.8480174"},{"key":"2021111418500509000_11.24.3482.32","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80451-3"},{"key":"2021111418500509000_11.24.3482.33","doi-asserted-by":"publisher","DOI":"10.1038\/nm1096-1132"},{"key":"2021111418500509000_11.24.3482.34","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.13.040195.000521"},{"key":"2021111418500509000_11.24.3482.35","doi-asserted-by":"publisher","DOI":"10.1126\/science.1621100"},{"key":"2021111418500509000_11.24.3482.36","doi-asserted-by":"publisher","DOI":"10.1210\/en.136.2.808"},{"key":"2021111418500509000_11.24.3482.37","first-page":"165","article-title":"Thymic epithelial antibodies: Immunohistochemical analysis and introduction of nomenclature.","volume":"13","author":"Kampinga","year":"1989","journal-title":"Thymus"},{"key":"2021111418500509000_11.24.3482.38","doi-asserted-by":"publisher","DOI":"10.1210\/en.136.7.3054"},{"key":"2021111418500509000_11.24.3482.39","doi-asserted-by":"publisher","DOI":"10.1038\/ng0895-435"},{"key":"2021111418500509000_11.24.3482.40","doi-asserted-by":"crossref","first-page":"2397","DOI":"10.1172\/JCI117606","article-title":"Interleukin-1 receptor antagonist and tumor necrosis factor binding protein decrease osteoclast formation and bone resorption in ovariectomized mice.","volume":"94","author":"Kitazawa","year":"1994","journal-title":"J. Clin. Invest."},{"key":"2021111418500509000_11.24.3482.41","doi-asserted-by":"crossref","first-page":"2341","DOI":"10.1128\/MCB.16.5.2341","article-title":"I\u03baB\u03b1 deficiency results in sustained NF-\u03baB response and severe widespread dermatitis in mice.","volume":"16","author":"Klement","year":"1996","journal-title":"Mol. Cell Biol."},{"key":"2021111418500509000_11.24.3482.42","doi-asserted-by":"publisher","DOI":"10.1101\/gad.9.16.1965"},{"key":"2021111418500509000_11.24.3482.43","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80373-6"},{"key":"2021111418500509000_11.24.3482.44","doi-asserted-by":"publisher","DOI":"10.1038\/383081a0"},{"key":"2021111418500509000_11.24.3482.45","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(94)90005-1"},{"key":"2021111418500509000_11.24.3482.46","first-page":"5349","article-title":"Sequential induction of NF-\u03baB \/Rel family proteins during B-cell terminal differentiation.","volume":"14","author":"Liou","year":"1994","journal-title":"Mol. Cell. Biol."},{"key":"2021111418500509000_11.24.3482.47","doi-asserted-by":"publisher","DOI":"10.1084\/jem.184.4.1207"},{"key":"2021111418500509000_11.24.3482.48","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81375-6"},{"key":"2021111418500509000_11.24.3482.49","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.10.4485"},{"key":"2021111418500509000_11.24.3482.50","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.12.040194.001001"},{"key":"2021111418500509000_11.24.3482.51","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1159\/000237496","article-title":"The development of lymphocytes.","volume":"113","author":"Melchers","year":"1997","journal-title":"Int. Arch. Allergy Immunol."},{"key":"2021111418500509000_11.24.3482.52","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1002\/jbmr.5650100202","article-title":"How many women have osteoporosis now?","volume":"10","author":"Melton","year":"1995","journal-title":"J. Bone Miner. Res."},{"key":"2021111418500509000_11.24.3482.53","doi-asserted-by":"crossref","first-page":"2828","DOI":"10.4049\/jimmunol.156.8.2828","article-title":"Regulation of 3\u2032IgH enhancers by a common set of factors, including \u03baB-binding proteins.","volume":"156","author":"Michaelson","year":"1996","journal-title":"J. Immunol."},{"key":"2021111418500509000_11.24.3482.54","doi-asserted-by":"publisher","DOI":"10.1007\/BF02411252"},{"key":"2021111418500509000_11.24.3482.55","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.11.5056"},{"key":"2021111418500509000_11.24.3482.56","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90030-G"},{"key":"2021111418500509000_11.24.3482.57","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(97)00653-4"},{"key":"2021111418500509000_11.24.3482.58","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.12.5134"},{"key":"2021111418500509000_11.24.3482.59","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/8756-3282(95)00347-4","article-title":"The heterogeneity of the osteopetroses reflects the diversity of cellular influences during skeletal development.","volume":"17","author":"Popoff","year":"1995","journal-title":"Bone"},{"key":"2021111418500509000_11.24.3482.60","doi-asserted-by":"publisher","DOI":"10.1038\/381751a0"},{"key":"2021111418500509000_11.24.3482.61","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.12.040194.003331"},{"key":"2021111418500509000_11.24.3482.62","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/S1074-7613(00)80271-X","article-title":"Corepression of RelA and c-Rel inhibits immunoglobulin kappa gene transcription and rearrangement in precursor B lymphocytes.","volume":"6","author":"Scherer","year":"1996","journal-title":"Immunity"},{"key":"2021111418500509000_11.24.3482.63","doi-asserted-by":"publisher","DOI":"10.1101\/gad.11.2.187"},{"key":"2021111418500509000_11.24.3482.64","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90415-8"},{"key":"2021111418500509000_11.24.3482.65","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80420-3"},{"key":"2021111418500509000_11.24.3482.66","doi-asserted-by":"publisher","DOI":"10.1126\/science.7526464"},{"key":"2021111418500509000_11.24.3482.67","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.10.1.405"},{"key":"2021111418500509000_11.24.3482.68","doi-asserted-by":"publisher","DOI":"10.1084\/jem.184.4.1537"},{"key":"2021111418500509000_11.24.3482.69","doi-asserted-by":"crossref","first-page":"183","DOI":"10.4049\/jimmunol.156.1.183","article-title":"B cells from p50\/NF-\u03baB knock-out mice have selective defects in proliferation, differentiation, germ-line CH transcription, and Ig class switching.","volume":"156","author":"Snapper","year":"1996","journal-title":"J. Immunol."},{"key":"2021111418500509000_11.24.3482.70","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90499-O"},{"key":"2021111418500509000_11.24.3482.71","doi-asserted-by":"publisher","DOI":"10.1084\/jem.176.2.495"},{"key":"2021111418500509000_11.24.3482.72","doi-asserted-by":"publisher","DOI":"10.1210\/endo-128-4-1792"},{"key":"2021111418500509000_11.24.3482.73","doi-asserted-by":"publisher","DOI":"10.1038\/386081a0"},{"key":"2021111418500509000_11.24.3482.74","doi-asserted-by":"publisher","DOI":"10.1038\/378298a0"},{"key":"2021111418500509000_11.24.3482.75","doi-asserted-by":"publisher","DOI":"10.1126\/science.274.5288.787"},{"key":"2021111418500509000_11.24.3482.76","doi-asserted-by":"publisher","DOI":"10.1101\/gad.9.22.2723"},{"key":"2021111418500509000_11.24.3482.77","doi-asserted-by":"publisher","DOI":"10.1126\/science.274.5288.784"},{"key":"2021111418500509000_11.24.3482.78","doi-asserted-by":"publisher","DOI":"10.1038\/360741a0"},{"key":"2021111418500509000_11.24.3482.79","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90416-6"},{"key":"2021111418500509000_11.24.3482.80","doi-asserted-by":"crossref","first-page":"3974","DOI":"10.4049\/jimmunol.157.9.3974","article-title":"Both multiorgan inflammation and myeloid hyperplasia in RelB-deficient mice are T cell dependent.","volume":"157","author":"Weih","year":"1996","journal-title":"J. Immunol."},{"key":"2021111418500509000_11.24.3482.81","doi-asserted-by":"publisher","DOI":"10.1084\/jem.185.7.1359"},{"key":"2021111418500509000_11.24.3482.82","doi-asserted-by":"crossref","first-page":"4682","DOI":"10.1002\/j.1460-2075.1996.tb00845.x","article-title":"Inhibition of NF-\u03baB\/Rel induces apoptosis of murine B cells.","volume":"15","author":"Wu","year":"1996","journal-title":"EMBO J."},{"key":"2021111418500509000_11.24.3482.83","doi-asserted-by":"publisher","DOI":"10.1038\/345442a0"}],"container-title":["Genes &amp; Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/gad.11.24.3482","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,16]],"date-time":"2023-05-16T15:42:06Z","timestamp":1684251726000},"score":1,"resource":{"primary":{"URL":"http:\/\/genesdev.cshlp.org\/lookup\/doi\/10.1101\/gad.11.24.3482"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,12,15]]},"references-count":83,"journal-issue":{"issue":"24","published-print":{"date-parts":[[1997,12,15]]}},"alternative-id":["10.1101\/gad.11.24.3482"],"URL":"https:\/\/doi.org\/10.1101\/gad.11.24.3482","relation":{},"ISSN":["0890-9369","1549-5477"],"issn-type":[{"value":"0890-9369","type":"print"},{"value":"1549-5477","type":"electronic"}],"subject":[],"published":{"date-parts":[[1997,12,15]]}}}