Altered surfactant function and structure in SP-A gene targeted mice.

TLDR

The surfactant protein A (SP‑A) gene was disrupted by homologous recombination in embryonic stem cells to generate homozygous SP‑A‑deficient mice. SP‑A knockout mice lack SP‑A mRNA and protein, show normal perinatal survival, lung morphology, surfactant protein composition, phospholipid pools, and compliance, but exhibit higher minimum surface tension at low surfactant concentrations and reduced tubular myelin, indicating that SP‑A is essential for tubular myelin formation without affecting overall pulmonary function.

Abstract

The surfactant protein A (SP-A) gene was disrupted by homologous recombination 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 composition, and lung compliance in SP-A(-/-) mice were unaltered. At the highest concentration tested, surfactant from SP-A(-/-) mice produced the same surface tension as (+/+) mice. At lower concentrations, minimum surface tensions were higher for SP-A(-/-) mice. At the ultrastructural level, type II cell morphology was the same in SP-A(+/+) and (-/-) mice. While alveolar phospholipid pool sizes were unperturbed, tubular 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 tubular myelin without detectably altering postnatal survival or pulmonary function.