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Targeted Disruption of TRAF3 Leads to Postnatal Lethality and Defective T-Dependent Immune Responses

Xu, Yang and Cheng, Genhong and Baltimore, David (1996) Targeted Disruption of TRAF3 Leads to Postnatal Lethality and Defective T-Dependent Immune Responses. Immunity, 5 (5). pp. 407-415. ISSN 1074-7613. doi:10.1016/s1074-7613(00)80497-5.

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TRAF3 was found as a protein that binds to the cytoplasmic tail of CD40 but is part of a family of proteins with common structure and activity. To clarify the physiological roles of TRAF3, we introduced a TRAF3 null mutation in mice through homologous recombination. TRAF3-deficient mice appear normal at birth but become progressively runted, correlating with progressive hypoglycemia and depletion of peripheral white cells. The mutant mice die by 10 days of age. Fetal liver cells from TRAF3-deficient embryos can reconstitute all hematopoietic lineages in lethally irradiated mice. However, these reconstituted mice are impaired in their immune responses to T-dependent antigen, and their T cells are functionally defective. These findings indicate that TRAF3 is required for postnatal development and for a competent immune system.

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Baltimore, David0000-0001-8723-8190
Additional Information:© 1996 Cell Press. Under an Elsevier user license. Received 22 August 1996, Revised 3 October 1996. Correspondence should be addressed to D. B. We thank Dr. R. Bronson for histological examinations of TRAF3^(−/−) mice, Dr. M. Scott for help with fetal liver transplant, L. Muglia for analysis of corticosteroid level, and Dr. M. Kehry for mCD40L. This project was supported by National Institutes of Health grants to D. B. Y. X. was supported by a postdoctoral fellowship from the Cancer Research Fund of the Damon Runyon–Walter Winchell Foundation. G. C. is a recipient of an Irvington House Institute fellowship. D. B. is an American Cancer Society Research professor.
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Damon Runyon Cancer Research FoundationUNSPECIFIED
Irvington Institute for Medical ResearchUNSPECIFIED
American Cancer SocietyUNSPECIFIED
Issue or Number:5
Record Number:CaltechAUTHORS:20200422-151000309
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Official Citation:Yang Xu, Genhong Cheng, David Baltimore, Targeted Disruption of TRAF3 Leads to Postnatal Lethality and Defective T-Dependent Immune Responses, Immunity, Volume 5, Issue 5, 1996, Pages 407-415, ISSN 1074-7613,
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:102737
Deposited By: George Porter
Deposited On:22 Apr 2020 22:53
Last Modified:16 Nov 2021 18:14

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