Surgical Murine Model of Congenital Diaphragmatic Hernia.

INTRODUCTION: Mouse models of congenital diaphragmatic hernia (CDH) are confounded by the teratogenic effects of nitrofen. Large animal surgical models are created later in lung development, making them less suitable to study the pathogenesis of pulmonary malformation. Therefore, we developed a surgical murine model of CDH that does not have the limitations of other models. Here we describe the feasibility of this model. METHODS: The fetuses of E16.5 pregnant C57BL/6 mice underwent thoracotomy and creation of a defect in the left hemidiaphragm. Littermates served as controls. A sham group underwent fetal thoracotomy without diaphragmatic defect creation. At E18.5, dams were euthanized. The fetal lungs were weighed, inflated, and subjected to histologic analysis. Analysis of variance was used for comparison between groups with P < 0.05 considered significant. RESULTS: Overall experimental survival was 58% with a successful CDH creation rate of 19%. Surgically induced CDH resulted in reduced total lung weight to body weight ratios (0.02 ± 0.004) compared to both sham (0.025 ± 0.004, P = 0.025) and control (0.026 ± 0.004, P = 0.003) groups. Fetuses with CDH also had lower airspace percentage (32.78 ± 17.1%) on histologic evaluation when compared to both sham (50.12 ± 10.2%, P = 0.046) and control (55.52 ± 1.4%, P = 0.009) groups. CONCLUSIONS: A surgical murine model of CDH is feasible and replicates the characteristic pulmonary findings of CDH without the confounding teratogenic effects of nitrofen.