Deciphering the Mechanisms Underlying Neuroendocrine Cell Hyperplasia of Infancy

项目总结 婴儿期神经内分泌细胞增生症(NEHI)是一种罕见的儿科肺部疾病，其特征是 慢性呼吸急促，需要补充氧气的低血氧饱和度，经常无法茁壮成长。一个 肺内神经内分泌细胞增多是NEHI的病理特征 活组织检查。然而，目前还不清楚是这种增加还是其他遗传或环境因素导致了这种疾病。 模仿在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 在携带这种患者突变的小鼠身上。我们的初步数据表明，这个模型概括了主要特征 这种疾病的危害。我们将使用该模型作为切入点来解决与NEHI相关的关键临床问题 发病机制。由于除了支持性护理之外，没有针对NEHI的特殊疗法，我们的发现可能会为我们提供信息 针对NEHI病的关键致病因素进行特定的药物治疗。

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.