Abnormal lung development and cleft palate in mice lacking TGF–β3 indicates defects of epithelial–mesenchymal interaction

A broad spectrum of biological activities has been proposed for transforming growth factor–β3(TGF–β 3). To study TGF–β3function in development, TGF–β3 null mutant mice were generated by gene–targeting. Within 20 hours of birth, homozygous TGF–β3−/− mice die with unique and consistent phenotypic features including delayed pulmonary development and defective palatogenesis. Unlike other null mutants with cleft palate, TGF–β3−/− mice lack other concomitant craniofacial abnormalities. This study demonstrates an essential function for TGF–β3 in the normal morphogenesis of palate and lung, and directly implicates this cytokine in mechanisms of epithelial–mesenchymal interaction.