RANK is essential for osteoclast and lymph node development

W C Dougall; M Glaccum; K Charrier; K Rohrbach; K Brasel; T De Smedt; E Daro; J Smith; M E Tometsko; C R Maliszewski; A Armstrong; V Shen; S Bain; D Cosman; D Anderson; P J Morrissey; J J Peschon; J Schuh

doi:10.1101/gad.13.18.2412

RANK is essential for osteoclast and lymph node development

Genes Dev. 1999 Sep 15;13(18):2412-24. doi: 10.1101/gad.13.18.2412.

Authors

W C Dougall¹, M Glaccum, K Charrier, K Rohrbach, K Brasel, T De Smedt, E Daro, J Smith, M E Tometsko, C R Maliszewski, A Armstrong, V Shen, S Bain, D Cosman, D Anderson, P J Morrissey, J J Peschon, J Schuh

Affiliation

¹ Immunex Corporation, Seattle, Washington 98101 USA. [email protected]

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.

MeSH terms

Animals
B-Lymphocytes / physiology
Bone Resorption / metabolism
Bone and Bones / diagnostic imaging
Carrier Proteins*
Dendritic Cells / physiology
Flow Cytometry
Gene Targeting
Hematopoiesis, Extramedullary / genetics
Hematopoietic Stem Cells / cytology
Lymph Nodes / embryology*
Macrophage Colony-Stimulating Factor / metabolism
Macrophages / physiology
Membrane Glycoproteins*
Mice
Mice, Inbred C57BL
Mice, Knockout
Osteoclasts / physiology*
Osteopetrosis / diagnostic imaging
Osteopetrosis / metabolism
Peyer's Patches / anatomy & histology
Phenotype
RANK Ligand
Radiography
Receptor Activator of Nuclear Factor-kappa B
Receptors, Tumor Necrosis Factor / genetics*
Receptors, Tumor Necrosis Factor / metabolism
Receptors, Tumor Necrosis Factor / physiology*
Spleen / anatomy & histology
Spleen / embryology

Substances

Carrier Proteins
Membrane Glycoproteins
RANK Ligand
Receptor Activator of Nuclear Factor-kappa B
Receptors, Tumor Necrosis Factor
Tnfrsf11a protein, mouse
Tnfsf11 protein, mouse
Macrophage Colony-Stimulating Factor