Altered surfactant function and structure in SP-A gene targeted mice
Altered surfactant function and structure in SP-A gene targeted mice
复制标题
DOI：
10.1073/pnas.93.18.9594
复制
发表时间：
1996-09-03
影响因子：
11.1
通讯作者：
Whitsett, JA
中科院分区：
文献类型：
--
作者：
Korfhagen, TR;Bruno, MD;Whitsett, JA
表面活性蛋白A(SP-A)基因在胚胎干细胞中的同源重组被破坏，用于产生纯合子的SP-A缺陷小鼠。SP-A(-/-)小鼠肺组织中未检测到SP-A基因和蛋白的表达，与野生型小鼠相比，SP-A(-/-)小鼠的围产期存活率无明显变化。SP-A(-/-)小鼠的肺形态、表面活性蛋白B-D、肺组织、肺泡磷脂池的大小和组成以及肺顺应性均未发生改变，在最高测试浓度下，SP-A(-/-)小鼠产生的表面张力与(+/+)小鼠相同。在较低浓度下，SP-A(-/-)小鼠的最小表面张力较高。在超微结构水平上，SP-A(+/+)和(-/-)小鼠的II型细胞形态相同。在肺泡磷脂池大小不受干扰的同时，SP-A(-/-)小鼠的肺小管髓鞘形态减少。小鼠SP-A基因的零突变干扰了管状髓鞘的形成，而不会明显改变出生后的存活率或肺功能。
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.