Lung Development in Congenital Diaphragmatic Hernia

先天性膈疝的肺部发育

• 批准号: 6679292
• 负责人: JANET E LARSON
• 金额: $ 6.83万
• 依托单位: OCHSNER CLINIC FOUNDATION
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6679292
• 关键词: animal mortality; cell differentiation; cell growth regulation; cell population study; cell proliferation; chloride channels; congenital disorders; diaphragm; electron microscopy; embryo /fetus therapy; epithelium; gene expression; gene therapy; hernia; laboratory rat; lung development; morphometry; nonhuman therapy evaluation

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.

描述（由申请人提供）：先天性腹股沟疝（CDH）与肺发育不全的结构异常有关。这些变化在除草醚诱导的CDH的啮齿动物模型中被模仿。硝草醚（2，4-二氯苯基-对-硝基苯醚）是一种除草剂，当在第9或10天喂食妊娠啮齿动物时，会在胎儿中产生疝气和/或肺发育不全。当用除草醚处理时，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（负责囊性纤维化的基因）进行基因治疗会导致上皮细胞增生和加速上皮细胞分化。研究者假设子宫内cftr基因治疗将减少与CDH相关的肺发育不全和上皮细胞不成熟。这一假设可以通过在妊娠9-10天用除草醚处理胎鼠，然后在妊娠16-17天进行子宫内基因治疗来检验。