TRANSGENIC MODELS FOR STUDY OF PULMONARY DEVELOPMENT AND DISEASE

This review summarizes progress in the application of transgenic mouse technology to the study of lung development and disease. Since advanc es in molecular genetics have greatly facilitated the isolation of cDN A and genes, our ability to readily assess roles of both normal and mu tated genes in transgenic mouse in vivo represents a major advance, br idging molecular biology and whole animal physiology. Strategies have been developed in which lung epithelial cell promoter elements are use d to drive normal or mutated genes into specific subsets of respirator y epithelial cells in the lungs of developing and mature transgenic mi ce. These mice have been used to elucidate cis-acting elements control ling lung epithelial cell gene expression, to discern the role of spec ific polypeptides in lung morphogenesis and tumorigenesis, and to crea te animal models of pulmonary disease. The ability to mutate genes at their precise chromosomal locations through gene targeting in embryoni c stem cells has lead to the production of animal models of lung disea ses such as cystic fibrosis. Both gene insertion and gene targeting cr eate permanent mouse lines that pass the modified gene to their progen y, providing animals for the study of the pathogenesis and treatment o f pulmonary disorders.