Lung Development in Congenital Diaphragmatic Hernia

描述(申请人提供)：先天性横隔疝(CDH)与肺发育不全的结构异常有关。这些变化在硝苯醚诱导的CDH啮齿动物模型中也得到了模拟。Nitrofen(2，4-二氯苯基-对-硝基苯基醚)是一种除草剂，当在第9天或第10天喂给怀孕的啮齿动物时，会在胎儿中产生横隔疝和/或肺发育不良。当使用硝苯醚治疗时，胎儿表现出上皮细胞不成熟和发育不全。 相反，研究人员发现，在子宫内使用CFTR(导致囊性纤维化的基因)的基因治疗会导致上皮细胞增殖和加速上皮细胞分化。研究人员假设，宫内基因治疗CFTR将减少与CDH相关的肺发育不良和上皮细胞未成熟。这一假设可以在胎鼠身上得到验证，方法是在怀孕9-10天用硝苯醚治疗，然后在怀孕16-17天用宫内基因治疗。

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.