POSTNATAL LUNG-FUNCTION AND MORPHOLOGY IN TRANSGENIC MICE EXPRESSING TRANSFORMING GROWTH-FACTOR-ALPHA

Developmental changes in lung morphology and physiology during postnat al alveolarization were assessed in transgenic mice expressing transfo rming growth factor-alpha (TGF-alpha) in pulmonary type II cells under control of the surfactant protein C gene promoter, TGF-alpha transcri pts were identified in respiratory epithelial cells at 1 day of age to adulthood. Enlargement of alveolar airspaces and fibrosis were detect ed as early as 1 week of age, and the increased airspace progressed wi th advancing age. Specific lung compliance was significantly increased in lungs of transgenic mice by 2 weeks of age and was associated with airflow obstruction. Chronic expression of TGF-alpha in the lungs of newborn transgenic mice caused remodeling of the developing lung durin g the period of postnatal alveolarization, resulting in markedly enlar ged parenchymal airspace, pulmonary fibrosis, and physiological abnorm alities including airway obstruction and increased lung compliance.