Deciphering the Mechanisms Underlying Neuroendocrine Cell Hyperplasia of Infancy

项目摘要 婴儿神经内分泌细胞增生症（NEHI）是一种罕见的儿科肺部疾病，其特征在于： 慢性呼吸急促、需要补充氧气的低血氧饱和度，以及经常无法茁壮成长。一 NEHI的病理学特征是观察到肺神经内分泌细胞增加 活组织检查然而，目前尚不清楚这种增加，或其他遗传或环境因素导致这种疾病。 模仿NEHI患者中发现的NKX2.1点突变，我们设计了第一个NEHI动物模型， 在携带这种病人突变的老鼠身上。我们的初步数据表明，该模型概括了关键特征， 疾病。我们将使用此模型作为切入点，以解决与NEHI相关的关键临床问题 发病机制由于除了支持性治疗外，NEHI没有特殊的治疗方法，我们的研究结果可能会为NEHI的治疗提供信息。 针对NEHI疾病关键致病因素的特异性药物治疗。

PROJECT SUMMARY Neuroendocrine Cell Hyperplasia of Infancy (NEHI) is a rare pediatric lung disease characterized by chronic tachypnea, low blood oxygen saturation requiring supplemental oxygen, and often failure to thrive. A defining pathological feature of NEHI is the observed increase of pulmonary neuroendocrine cells in lung biopsies. However, it is unknown if this increase, or other genetic or environmental factors cause the disease. Mimicking an NKX2.1 point mutation identified in NEHI patients, we engineered the first animal model of NEHI in mice carrying this patient mutation. Our preliminary data indicate that this model recapitulates key features of the disease. We will use this model as an entry point to address key clinical questions associated with NEHI pathogenesis. As there is no particular therapy for NEHI beyond supportive care, our findings may inform specific pharmacological therapy targeting the key NEHI disease causal factors.