TRAF4 deficiency leads to tracheal malformation with resulting alterationsin air flow to the lungs

TRAF4 Is one of six identified members of the family of TNFR-associated fac tors. While the other family members have been found to play important role s in the development and maintenance of a normal immune system, the importa nce of TRAF4 has remained unclear. To address this issue, we have generated TRAF4-deficient mice. Despite widespread expression of TRAF4 in the develo ping embryo, as well as in the adult, lack of TRAF4 expression results in a localized, developmental defect of the upper respiratory tract. TRAF4-defi cient mice are born with a constricted upper trachea at the site of the tra cheal junction with the larynx. This narrowing of the proximal end of the t rachea results in respiratory air flow abnormalities and increases rates of pulmonary inflammation. These data demonstrate that TRAF4 is required to r egulate the anastomosis of the upper and lower respiratory systems during d evelopment.