Respiratory Deficiencies in Congenital Diaphragmatic Hernia

 描述(由申请人提供)：先天性横隔性疝气(CDH)是一种常见的出生缺陷，与显著的死亡率有关。CDH新生儿死亡的主要原因是肺功能不足。那些存活下来的人更容易患上哮喘和肺动脉高压。一种流行的观点认为CDH的病因是由横隔膜畸形引起的，从而使腹部器官进入胸部，压迫肺。我们提供了来自CDH小鼠遗传模型的数据，该模型表明疾病的起源与横隔膜无关。我们建议使用这些模型来揭示主要原因，追踪疾病进展，并识别发病过程中的新节点，在这些节点中，知情的临床干预将增加生存率和降低发病率。

 DESCRIPTION (provided by applicant): Congenital Diaphragmatic Hernia (CDH) is a common birth defect that is associated with a significant mortality rate. CDH newborns die largely because of insufficient lung function. Those that do survive are more susceptible to developing asthma and pulmonary hypertension. A popular view of the cause of CDH is that it arises from diaphragm malformations, which then allows abdominal organs into the chest, compressing the lung. We present data from mouse genetic models of CDH that demonstrate diaphragm-independent origins of disease. We propose to use these models to uncover the primary cause, trace disease progression, and identify novel nodes of the pathogenesis process where informed clinical interventions would increase survival and decrease morbidities.