RANK is essential for osteoclast and lymph node development

William C. Dougall; Moira Glaccum; K Charrier; Kathy Rohrbach; Kenneth Brasel; Thibaut De Smedt; Elizabeth Daro; J. A. Smith; Mark Tometsko; C R Maliszewski; Allison Armstrong; V. Shen; Steven D. Bain; David Cosman; Dirk Anderson; Philip Morrissey; Jacques J. Peschon; JoAnn C. L. Schuh

doi:10.1101/gad.13.18.2412

Abstract

The physiological role of the TNF receptor (TNFR) family member, RANK, was investigated by generating RANK-deficient mice. RANK(-/-) mice were characterized by profound osteopetrosis resulting from an apparent block in osteoclast differentiation. RANK expression was not required for the commitment, differentiation, and functional maturation of macrophages and dendritic cells from their myeloid precursors but provided a necessary and specific signal for the differentiation of myeloid-derived osteoclasts. RANK(-/-) mice also exhibited a marked deficiency of B cells in the spleen. RANK(-/-) mice retained mucosal-associated lymphoid tissues including Peyer's patches but completely lacked all other peripheral lymph nodes, highlighting an additional major role for RANK in lymph node formation. These experiments reveal that RANK provides critical signals necessary for lymph node organogenesis and osteoclast differentiation.

Keywords

BiologyOsteoclastLymph nodeRANK LigandRank (graph theory)Cell biologyLymphCellular differentiationImmunologySpleenLymph node stromal cellCancer researchReceptorPathologyGeneCombinatoricsGeneticsRANKLMedicineMathematics

Affiliated Institutions

IDEX Corporation (United States) US

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Publication Info

Year: 1999
Type: article
Volume: 13
Issue: 18
Pages: 2412-2424
Citations: 1474
Access: Closed

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APA Style

                            
                                
                                    William C. Dougall, 
                                
                                    Moira Glaccum, 
                                
                                    K Charrier
                                
                                et al.
                            
                            (1999). 
                            RANK is essential for osteoclast and lymph node development. 
                            Genes & Development
                            , 13
                            (18)
                            , 2412-2424.
                            https://doi.org/10.1101/gad.13.18.2412
                        

Identifiers

DOI: 10.1101/gad.13.18.2412