This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Shiels, H. Articles by Lindsten, T. Search for Related Content PubMed PubMed Citation Articles by Shiels, H. Articles by Lindsten, T.

(American Journal of Pathology. 2000;157:679-688.)
© 2000 American Society for Investigative Pathology

Animal Models

TRAF4 Deficiency Leads to Tracheal Malformation with Resulting Alterations in Air Flow to the Lungs

Helena Shiels^*, Xiantang Li, Paul T. Schumacker^§, Emin Maltepe^§¶, Philip A. Padrid^§, Anne Sperling^§, Craig B. Thompson^*§¶ and Tullia Lindsten^*§

From the Gwen Knapp Center for Lupus and Immunology Research,^*
the Committee on Immunology,
the Department of Pathology,
and the Department of Medicine,^§
Howard Hughes Medical Institute,^¶
University of Chicago, Chicago, Illinois

TRAF4 is one of six identified members of the family of TNFR-associated factors. While the other family members have been found to play important roles in the development and maintenance of a normal immune system, the importance of TRAF4 has remained unclear. To address this issue, we have generated TRAF4-deficient mice. Despite widespread expression of TRAF4 in the developing embryo, as well as in the adult, lack of TRAF4 expression results in a localized, developmental defect of the upper respiratory tract. TRAF4-deficient mice are born with a constricted upper trachea at the site of the tracheal junction with the larynx. This narrowing of the proximal end of the trachea results in respiratory air flow abnormalities and increases rates of pulmonary inflammation. These data demonstrate that TRAF4 is required to regulate the anastomosis of the upper and lower respiratory systems during development.

This article has been cited by other articles:

				E. Bonvin, P. Le Rouzic, J.-F. Bernaudin, C.-H. Cottart, C. Vandebrouck, A. Crie, T. Leal, A. Clement, and M. Bonora Congenital tracheal malformation in cystic fibrosis transmembrane conductance regulator-deficient mice J. Physiol., July 1, 2008; 586(13): 3231 - 3243. [Abstract] [Full Text] [PDF]

				S. M. Bell, C. M. Schreiner, S. E. Wert, M. L. Mucenski, W. J. Scott, and J. A. Whitsett R-spondin 2 is required for normal laryngeal-tracheal, lung and limb morphogenesis Development, March 15, 2008; 135(6): 1049 - 1058. [Abstract] [Full Text] [PDF]

				W. V. Cardoso and J. Lu Regulation of early lung morphogenesis: questions, facts and controversies Development, May 1, 2006; 133(9): 1611 - 1624. [Abstract] [Full Text] [PDF]

				E. M. Esparza, T. Lindsten, J. M. Stockhausen, and R. H. Arch Tumor Necrosis Factor Receptor (TNFR)-associated Factor 5 Is a Critical Intermediate of Costimulatory Signaling Pathways Triggered by Glucocorticoid-induced TNFR in T Cells J. Biol. Chem., March 31, 2006; 281(13): 8559 - 8564. [Abstract] [Full Text] [PDF]

				T. M. Zimmerman, H. Harlin, O. M. Odenike, S. Berk, E. Sprague, T. Karrison, W. Stock, R. A. Larson, M. J. Ratain, and T. F. Gajewski Dose-Ranging Pharmacodynamic Study of Tipifarnib (R115777) in Patients With Relapsed and Refractory Hematologic Malignancies J. Clin. Oncol., December 1, 2004; 22(23): 4816 - 4822. [Abstract] [Full Text] [PDF]

				J. K. Sax and W. S. El-Deiry Identification and Characterization of the Cytoplasmic Protein TRAF4 as a p53-regulated Proapoptotic Gene J. Biol. Chem., September 19, 2003; 278(38): 36435 - 36444. [Abstract] [Full Text] [PDF]

				C. J. Zeiss The Apoptosis-Necrosis Continuum: Insights from Genetically Altered Mice Vet. Pathol., September 1, 2003; 40(5): 481 - 495. [Abstract] [Full Text] [PDF]

				F. Henkler, B. Baumann, M. Fotin-Mleczek, M. Weingartner, R. Schwenzer, N. Peters, A. Graness, T. Wirth, P. Scheurich, J. A. Schmid, et al. Caspase-mediated Cleavage Converts the Tumor Necrosis Factor (TNF) Receptor-associated Factor (TRAF)-1 from a Selective Modulator of TNF Receptor Signaling to a General Inhibitor of NF-{kappa}B Activation J. Biol. Chem., August 1, 2003; 278(31): 29216 - 29230. [Abstract] [Full Text] [PDF]

				Y. C. Xu, R. F. Wu, Y. Gu, Y.-S. Yang, M.-C. Yang, F. E. Nwariaku, and L. S. Terada Involvement of TRAF4 in Oxidative Activation of c-Jun N-terminal Kinase J. Biol. Chem., July 26, 2002; 277(31): 28051 - 28057. [Abstract] [Full Text] [PDF]

				C. H. Regnier, R. Masson, V. Kedinger, J. Textoris, I. Stoll, M.-P. Chenard, A. Dierich, C. Tomasetto, and M.-C. Rio Impaired neural tube closure, axial skeleton malformations, and tracheal ring disruption in TRAF4-deficient mice PNAS, April 16, 2002; 99(8): 5585 - 5590. [Abstract] [Full Text] [PDF]

				J. Y. Chung, Y. C. Park, H. Ye, and H. Wu All TRAFs are not created equal: common and distinct molecular mechanisms of TRAF-mediated signal transduction J. Cell Sci., February 15, 2002; 115(4): 679 - 688. [Abstract] [Full Text] [PDF]

				H. Harlin, S. B. Reffey, C. S. Duckett, T. Lindsten, and C. B. Thompson Characterization of XIAP-Deficient Mice Mol. Cell. Biol., May 15, 2001; 21(10): 3604 - 3608. [Abstract] [Full Text]

				C. H. Regnier, R. Masson, V. Kedinger, J. Textoris, I. Stoll, M.-P. Chenard, A. Dierich, C. Tomasetto, and M.-C. Rio Impaired neural tube closure, axial skeleton malformations, and tracheal ring disruption in TRAF4-deficient mice PNAS, April 16, 2002; 99(8): 5585 - 5590. [Abstract] [Full Text] [PDF]