PMID- 10421844
OWN - NLM
STAT- MEDLINE
DCOM- 19991014
LR  - 20191103
IS  - 1356-9597 (Print)
IS  - 1356-9597 (Linking)
VI  - 4
IP  - 6
DP  - 1999 Jun
TI  - Severe osteopetrosis, defective interleukin-1 signalling and lymph node
      organogenesis in TRAF6-deficient mice.
PG  - 353-62
AB  - BACKGROUND: TRAF6, a member of the tumour necrosis factor receptor-associated
      factor family, was first identified as a transducer of CD40 and interleukin-1
      receptor (IL-1R) signals based on the interaction of TRAF6 with the cytoplasmic
      tail of CD40 and with the IL-1R associated kinase in vitro. However, the
      functions of TRAF6 in vivo remain unidentified. RESULTS: We show that TRAF6-/-
      mice exhibit severe osteopetrosis and are defective in osteoclast formation. In
      vitro culture experiments revealed that osteoclast precursor cells derived from
      TRAF6-/- mice are unable to differentiate to functional osteoclasts in response
      to osteoclast differentiation factor (ODF). In bone marrow of TRAF6-/- mice, the 
      number of sIgM+B220+ immature B cells is markedly reduced while the ratio of proB
      to preB cells is not affected. In contrast, development of thymocytes is not
      affected. Furthermore, TRAF6-/- mice are defective in lymph node organogenesis
      and IL-1 signalling in thymocytes. CONCLUSIONS: The results identify TRAF6 as an 
      essential component of ODF signalling pathway, and also show that TRAF6 plays
      pivotal roles in immune and inflammatory systems in vivo.
FAU - Naito, A
AU  - Naito A
AD  - Department of Oncology, The Institute of Medical Science, The University of
      Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
FAU - Azuma, S
AU  - Azuma S
FAU - Tanaka, S
AU  - Tanaka S
FAU - Miyazaki, T
AU  - Miyazaki T
FAU - Takaki, S
AU  - Takaki S
FAU - Takatsu, K
AU  - Takatsu K
FAU - Nakao, K
AU  - Nakao K
FAU - Nakamura, K
AU  - Nakamura K
FAU - Katsuki, M
AU  - Katsuki M
FAU - Yamamoto, T
AU  - Yamamoto T
FAU - Inoue, J
AU  - Inoue J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Genes Cells
JT  - Genes to cells : devoted to molecular & cellular mechanisms
JID - 9607379
RN  - 0 (Interleukin-1)
RN  - 0 (Proteins)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (TNF Receptor-Associated Factor 6)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells/cytology
MH  - Cell Differentiation
MH  - Embryonic and Fetal Development
MH  - Interleukin-1/*metabolism
MH  - Lymph Nodes/*embryology
MH  - Mice
MH  - Mice, Knockout
MH  - Osteoclasts/cytology
MH  - Osteopetrosis/*genetics
MH  - Proteins/*genetics/metabolism
MH  - Receptors, Tumor Necrosis Factor/metabolism
MH  - Signal Transduction/*genetics
MH  - Spleen/cytology
MH  - TNF Receptor-Associated Factor 6
EDAT- 1999/07/28 00:00
MHDA- 1999/07/28 00:01
CRDT- 1999/07/28 00:00
PHST- 1999/07/28 00:00 [pubmed]
PHST- 1999/07/28 00:01 [medline]
PHST- 1999/07/28 00:00 [entrez]
AID - gtc265 [pii]
AID - 10.1046/j.1365-2443.1999.00265.x [doi]
PST - ppublish
SO  - Genes Cells. 1999 Jun;4(6):353-62. doi: 10.1046/j.1365-2443.1999.00265.x.