TRAF4 deficiency leads to tracheal malformation with resulting alterations in air flow to the lungs.
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.
Shiels
H
H
Gwen Knapp Center for Lupus and Immunology Research, the Committee on Immunology, the Department of Pathology, Howard Hughes Medical Institute, University of Chicago, Chicago, Illinois, USA.
Li
X
X
Schumacker
P T
PT
Maltepe
E
E
Padrid
P A
PA
Sperling
A
A
Thompson
C B
CB
Lindsten
T
T
D000818:Animals; D004195:Disease Models, Animal; D018390:Gene Targeting; D006801:Humans; D007830:Larynx / Q000196:embryology / Q000503:physiopathology; D008168:Lung / Q000196:embryology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012120:Respiration Disorders / Q000235:genetics / Q000503:physiopathology; D053449:TNF Receptor-Associated Factor 4; D014132:Trachea / Q000002:abnormalities* / Q000196:embryology / Q000503:physiopathology; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
D011506:Proteins; D053449:TNF Receptor-Associated Factor 4; C506367:TRAF4 protein, human; C506368:Traf4 protein, mouse; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins