Altered Surfactant Function and Structure in SP-A Gene Targeted Mice

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 compare...

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Veröffentlicht in:Proceedings of the National Academy of Sciences - PNAS 1996-09, Vol.93 (18), p.9594-9599
Hauptverfasser: Korfhagen, Thomas R., Bruno, Michael D., Ross, Gary F., Huelsman, Karen M., Ikegami, Machiko, Jobe, Alan H., Wert, Susan E., Stripp, Barry R., Morris, Randal E., Glasser, Stephan W., Bachurski, Cindy J., Iwamoto, Harriet S., Whitsett, Jeffrey A.
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Sprache:eng
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Zusammenfassung: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.93.18.9594