RANK is essential for osteoclast and lymph node development.
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.
Dougall
W C
WC
Immunex Corporation, Seattle, Washington 98101 USA. wdougall@immunex.com
Glaccum
M
M
Charrier
K
K
Rohrbach
K
K
Brasel
K
K
De Smedt
T
T
Daro
E
E
Smith
J
J
Tometsko
M E
ME
Maliszewski
C R
CR
Armstrong
A
A
Shen
V
V
Bain
S
S
Cosman
D
D
Anderson
D
D
Morrissey
P J
PJ
Peschon
J J
JJ
Schuh
J
J
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology; D001862:Bone Resorption / Q000378:metabolism; D001842:Bone and Bones / Q000000981:diagnostic imaging; D002352:Carrier Proteins; D003713:Dendritic Cells / Q000502:physiology; D005434:Flow Cytometry; D018390:Gene Targeting; D006411:Hematopoiesis, Extramedullary / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000166:cytology; D008198:Lymph Nodes / Q000196:embryology*; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D008264:Macrophages / Q000502:physiology; D008562:Membrane Glycoproteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010010:Osteoclasts / Q000502:physiology*; D010022:Osteopetrosis / Q000000981:diagnostic imaging / Q000378:metabolism; D010581:Peyer's Patches / Q000033:anatomy & histology; D010641:Phenotype; D053245:RANK Ligand; D011859:Radiography; D053246:Receptor Activator of Nuclear Factor-kappa B; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D013154:Spleen / Q000033:anatomy & histology / Q000196:embryology
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018124:Receptors, Tumor Necrosis Factor; C505687:Tnfrsf11a protein, mouse; C505689:Tnfsf11 protein, mouse; D016173:Macrophage Colony-Stimulating Factor