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

被引:343
作者
Korfhagen, TR
Bruno, MD
Ross, GF
Huelsman, KM
Ikegami, M
Jobe, AH
Wert, SE
Stripp, BR
Morris, RE
Glasser, SW
Bachurski, CJ
Iwamoto, HS
Whitsett, JA
机构
[1] CHILDRENS HOSP,MED CTR,DEPT PEDIAT,CINCINNATI,OH 45229
[2] UNIV CALIF LOS ANGELES,HARBOR MED CTR,DEPT PEDIAT,TORRANCE,CA 90509
关键词
D O I
10.1073/pnas.93.18.9594
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:9594 / 9599
页数:6
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