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Molecular and Cellular Biology, May 2001, p. 3451-3461, Vol. 21, No. 10
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.10.3451-3461.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
DR3 Regulates Negative Selection during
Thymocyte Development
Eddie C. Y.
Wang,1,
Anette
Thern,1
Angela
Denzel,1
Jeremy
Kitson,2
Stuart N.
Farrow,2 and
Michael J.
Owen1,*
Imperial Cancer Research Fund, Lincoln's Inn
Fields, London WC2A 3PX,1 and Glaxo
Wellcome, Stevenage, Herts SG1 2NY,2 United
Kingdom
Received 16 October 2000/Returned for modification 6 December
2000/Accepted 22 February 2001
DR3 (Ws1, Apo3, LARD, TRAMP, TNFSFR12) is a member of the death
domain-containing tumor necrosis factor receptor (TNFR) superfamily, members of which mediate a variety of developmental events including the regulation of cell proliferation, differentiation, and apoptosis. We have investigated the in vivo role(s) of DR3 by generating mice
congenitally deficient in the expression of the DR3 gene. We show that
negative selection and anti-CD3-induced apoptosis are significantly
impaired in DR3-null mice. In contrast, both superantigen-induced
negative selection and positive selection are normal. The pre-T-cell
receptor-mediated checkpoint, which is dependent on TNFR signaling, is
also unaffected in DR3-deficient mice. These data reveal a nonredundant
in vivo role for this TNF receptor family member in the removal of
self-reactive T cells in the thymus.
*
Corresponding author. Mailing address: Imperial Cancer
Research Fund, P.O. Box 123, Lincoln's Inn Fields, London, WC2A 3PX, United Kingdom. Phone: 44 020 7269 3069. Fax: 44 020 7269 3479 E-mail:
m.owen{at}icrf.icnet.uk.

Present address: Department of Medicine, University of Wales
College of Medicine, Heath Park, Cardiff CF14 4XX, United
Kingdom.
Molecular and Cellular Biology, May 2001, p. 3451-3461, Vol. 21, No. 10
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.10.3451-3461.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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