Normal lung development and function after Sox9 inactivation in the respiratory epithelium
Normal lung development and function after Sox9 inactivation in the respiratory epithelium
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DOI：
10.1002/gene.20093
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发表时间：
2005-01-01
期刊：
影响因子：
1.5
通讯作者：
Whitsett, JA
中科院分区：
文献类型：
--
作者：
Perl, AKT;Kist, R;Whitsett, JA
人类S 0X 9基因中的杂合突变导致肢端发育不良（CID），一种伴有各种其他器官缺陷的骨骼畸形综合征。严重感染的CID患者通常在新生儿期因呼吸窘迫而死亡。我们分析了Sox 9在整个形态发生过程中在发育小鼠肺中的动态表达模式。为了确定Sox 9在肺发育和功能中的作用，使用多西环素诱导的Cre/IoxP系统在小鼠肺的呼吸道上皮细胞中特异性灭活Sox 9。免疫组织化学和RNA分析表明，早在胚胎第12.5天，Sox 9就在肺发育的胚胎阶段广泛失活。出生后的肺形态发生和肺功能没有改变。未检测到Sox 2、Sox 4、Sox 8、Sox 10、Sox 11和Sox 17的补偿性上调。尽管Sox 9在整个肺形态发生中以高水平表达，但呼吸道上皮细胞的Sox 9失活不会改变肺结构、出生后存活或氧损伤后的修复。(C)2005 Wiley-Liss，Inc.
Heterozygous mutations in the human SOX9 gene cause campomelic dysplasia (CID), a skeletal malformation syndrome with various other organ defects. Severely affected CID patients usually die in the neonatal period due to respiratory distress. We analyzed the dynamic expression pattern of Sox9 in the developing mouse lung throughout morphogenesis. To determine a role of Sox9 in lung development and function, Sox9 was specifically inactivated in respiratory epithelial cells of the mouse lung using a doxycycline-inducible Cre/IoxP system. Immunohistochemical and RNA analysis demonstrated extensive inactivation of Sox9 in the embryonic stage of lung development as early as embryonic day (E) 12.5. Lung morphogenesis and lung function after birth were not altered. Compensatory upregulation of Sox2, Sox4, Sox8, Sox10, Sox11, and Sox17 was not detected. Although Sox9 is expressed at high levels throughout lung morphogenesis, inactivation of Sox9 from the respiratory epithelial cells does not alter lung structure, postnatal survival, or repair following oxygen injury. (C) 2005 Wiley-Liss, Inc.