ALTERED SURFACTANT FUNCTION AND STRUCTURE IN SP-A GENE TARGETED MICE

The surfactant protein A (SP-A) gene was disrupted by homologous recom bination in embryonic stem cells that were used to generate homozygous SP-A-deficient mice. SP-A mRNA and protein were not detectable in the lungs of SP-A(-/-) mice, and perinatal survival of SP-A(-/-) mice was not altered compared with wild-type mice. Lung morphology, surfactant proteins B-D, lung tissue, alveolar phospholipid pool sizes and compo sition, and lung compliance in SP-A(-/-) mice were unaltered, At the h ighest concentration tested, surfactant from SP-A(-/-) mice produced t he same surface tension as (+/+) mice. At lower concentrations, minimu m surface tensions were higher for SP-A(-/-) mice. At the ultrastructu ral level, type II cell morphology was the same in SP-A(+/+) and (-/-) mice. While alveolar phospholipid pool sizes were unperturbed, tubula r myelin figures were decreased in the lungs of SP-A(-/-) mice. A null mutation of the murine SP-A gene interferes with the formation of tub ular myelin without detectably altering postnatal survival or pulmonar y function.