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.
| Larson, Janet E; Cohen, J Craig (2006) Improvement of pulmonary hypoplasia associated with congenital diaphragmatic hernia by in utero CFTR gene therapy. Am J Physiol Lung Cell Mol Physiol 291:L4-10 |
