ABNORMAL LUNG DEVELOPMENT AND CLEFT-PALATE IN MICE LACKING TGF-BETA-3INDICATES DEFECTS OF EPITHELIAL-MESENCHYMAL INTERACTION

A broad spectrum of biological activities has been proposed for transf orming growth factor-beta 3 (TGF-beta 3). To study TGF-beta 3 function in development, TGF-beta 3 null mutant mice were generated by gene-ta rgeting. Within 20 hours of birth, homozygous TGF-beta 3 -/- mice die with unique and consistent phenotypic features including delayed pulmo nary development and defective palatogenesis. Unlike other null mutant s with cleft palate, TGF-beta 3 -/- mice lack other concomitant cranio facial abnormalities. This study demonstrates an essential function fo r TGF-beta 3 in the normal morphogenesis of palate and lung, and direc tly implicates this cytokine in mechanisms of epithelial-mesenchymal i nteraction.