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

T R Korfhagen; M D Bruno; G F Ross; K M Huelsman; M Ikegami; A H Jobe; S E Wert; B R Stripp; R E Morris; S W Glasser; C J Bachurski; H S Iwamoto; J A Whitsett

doi:10.1073/pnas.93.18.9594

PubMed · 8790375

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

T R Korfhagen·M D Bruno·G F Ross·K M Huelsman·M Ikegami·A H Jobe·S E Wert·B R Stripp·R E Morris·S W Glasser·C J Bachurski·H S Iwamoto·J A Whitsett

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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.

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Animals Blotting, Southern Gene Targeting Genotype Glycoproteins Mice Mutagenesis, Site-Directed Phospholipids Proteolipids Pulmonary Alveoli Pulmonary Surfactant-Associated Protein A Pulmonary Surfactant-Associated Proteins Pulmonary Surfactants RNA, Messenger Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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T R Korfhagen, M D Bruno, G F Ross, K M Huelsman, M Ikegami, A H Jobe, S E Wert, B R Stripp, R E Morris, S W Glasser, C J Bachurski, H S Iwamoto, J A Whitsett. 1996-09-03. Altered surfactant function and structure in SP-A gene targeted mice.. https://doi.org/10.1073/pnas.93.18.9594

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