Lung Development in Congenital Diaphragmatic Hernia

描述（由申请人提供）：先天性膈疝（CDH）与肺发育不全的结构异常有关。这些变化在硝芬诱导的CDH啮齿动物模型中被模拟。硝基芬（2,4-二氯苯-对硝基苯基醚）是一种除草剂，当在第9天或第10天给怀孕的啮齿动物喂食时，会造成胎儿膈疝和/或肺发育不全。当用硝芬处理时，胎儿表现出上皮细胞不成熟和发育不全。

DESCRIPTION (provided by applicant): Congenital diaphragmatic hernia (CDH) is associated with the structural abnormality of pulmonary hypoplasia. These changes are mimicked in the rodent model of nitrofen-induced CDH. Nitrofen (2,4-dichlorophenyl-p-nitrophenyl ether) is an herbicide that when fed to a pregnant rodent at day 9 or 10 creates diaphragmatic hernia and/or lung hypoplasia in the fetuses. When treated with nitrofen the fetuses demonstrate epithelial cell immaturity as well as hypoplasia. In contrast, the investigators have found that in utero gene therapy with CFTR (the gene responsible for Cystic Fibrosis) results in epithelial cell hyperplasia and accelerated epithelial cell differentiation. The investigators hypothesize that in utero gene therapy with cftr will reduce the pulmonary hypoplasia and epithelial cell immaturity associated with CDH. This hypothesis can be tested in the fetal rat by treatment with nitrofen at 9-10 days gestation followed by in utero gene therapy at 16-17 days gestation.