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SP-A基因靶向小鼠中表面活性剂功能和结构的改变

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

作者信息

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

机构信息

Children's Hospital Medical Center, Department of Pediatrics, Cincinnati, OH 45229-3039, USA.

出版信息

Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9594-9. doi: 10.1073/pnas.93.18.9594.

DOI:10.1073/pnas.93.18.9594
PMID:8790375
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC38473/
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.

摘要

表面活性蛋白A(SP-A)基因在胚胎干细胞中通过同源重组被破坏,这些胚胎干细胞被用于培育纯合SP-A缺陷小鼠。在SP-A(-/-)小鼠的肺中检测不到SP-A mRNA和蛋白,并且与野生型小鼠相比,SP-A(-/-)小鼠围产期存活率没有改变。SP-A(-/-)小鼠的肺形态、表面活性蛋白B-D、肺组织、肺泡磷脂池大小和组成以及肺顺应性均未改变。在测试的最高浓度下,来自SP-A(-/-)小鼠的表面活性剂产生的表面张力与(+/+)小鼠相同。在较低浓度下,SP-A(-/-)小鼠的最小表面张力更高。在超微结构水平上,SP-A(+/+)和(-/-)小鼠的II型细胞形态相同。虽然肺泡磷脂池大小未受干扰,但SP-A(-/-)小鼠肺中的管状髓磷脂结构减少。小鼠SP-A基因的无效突变会干扰管状髓磷脂的形成,而不会明显改变出生后的存活率或肺功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cf5/38473/5004139d9ec0/pnas01522-0309-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cf5/38473/68bc53812672/pnas01522-0306-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cf5/38473/c568c253cdfb/pnas01522-0307-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cf5/38473/eaebe40d9655/pnas01522-0307-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cf5/38473/2bee6d108bce/pnas01522-0307-c.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cf5/38473/5004139d9ec0/pnas01522-0309-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cf5/38473/68bc53812672/pnas01522-0306-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cf5/38473/c568c253cdfb/pnas01522-0307-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cf5/38473/eaebe40d9655/pnas01522-0307-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cf5/38473/2bee6d108bce/pnas01522-0307-c.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2cf5/38473/5004139d9ec0/pnas01522-0309-a.jpg

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本文引用的文献

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