Early lethality, functional NF-kappaB activation, and increased sensitivity to TNF-induced cell death in TRAF2-deficient mice - PubMed (original) (raw)

doi: 10.1016/s1074-7613(00)80391-x.

A Shahinian, D Speiser, J Kraunus, F Billia, A Wakeham, J L de la Pompa, D Ferrick, B Hum, N Iscove, P Ohashi, M Rothe, D V Goeddel, T W Mak

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• PMID: 9390694
• DOI: 10.1016/s1074-7613(00)80391-x

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Early lethality, functional NF-kappaB activation, and increased sensitivity to TNF-induced cell death in TRAF2-deficient mice

W C Yeh et al. Immunity. 1997 Nov.

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Abstract

TRAF2 is an intracellular signal-transducing protein recruited to the TNFR1 and TNFR2 receptors following TNF stimulation. To investigate the physiological role of TRAF2, we generated TRAF2-deficient mice. traf2-/- mice appeared normal at birth but became progressively runted and died prematurely. Atrophy of the thymus and spleen and depletion of B cell precursors also were observed. Thymocytes and other hematopoietic progenitors were highly sensitive to TNF-induced cell death and serum TNF levels were elevated in these TRAF2-deficient animals. Examination of traf2-/- cells revealed a severe reduction in TNF-mediated JNK/SAPK activation but a mild effect on NF-kappaB activation. These results suggest that TRAF2-independent pathways of NF-kappaB activation exist and that TRAF2 is required for an NF-kappaB-independent signal that protects against TNF-induced apoptosis.

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