TARGETED DISRUPTION OF THE SURFACTANT PROTEIN-B GENE DISRUPTS SURFACTANT HOMEOSTASIS, CAUSING RESPIRATORY-FAILURE IN NEWBORN MICE

Surfactant protein B (SP-B) is an 8.7-kDa, hydrophobic protein that en hances the spreading and stability of surfactant phospholipids in the alveolus. To further assess the role of SP-B in lung function, the SP- B gene was disrupted by homologous recombination in murine mouse embry onic stem cells, Mice with a single mutated SP-B allele (+/-) were una ffected, whereas homozygous SP-B -/- offspring died of respiratory fai lure immediately after birth. Lungs of SP-B -/- mice developed normall y but remained atelectatic in spite of postnatal respiratory efforts, SP-B protein and mRNA were undetectable and tubular myelin figures wer e lacking in SP-B -/- mice, Type II cells of SP-B -/- mice contained n o fully formed lamellar bodies. While the abundance of SP-A and SP-C m RNAs was mt altered, an aberrant form of pro-SP-C, 8.5 kDa, was detect ed, and fully processed SP-C peptide was markedly decreased in lung ho mogenates of SP-B -/- mice, Ablation of the SP-B gene disrupts the rou ting, storage, and function of surfactant phospholipids and proteins, causing respiratory failure at birth.