Deciphering the Mechanisms Underlying Neuroendocrine Cell Hyperplasia of Infancy

破译婴儿期神经内分泌细胞增生的机制

基本信息

批准号：
10390311
负责人：
Xin Sun
金额：
$ 54.57万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-01 至 2023-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10390311
关键词：
Address Aerosols Affect Air Alleles Allergens Alveolar Amines Animal Model Archives Biological Assay Biopsy Birth Blood Blood capillaries Body Weight Bronchoalveolar Lavage Fluid CRISPR/Cas technology Cell Count Cells Characteristics Child Childhood Chronic Clinical DNA Binding Domain Data Defect Dense Core Vesicle Disease Dyes Edema Engineering Environment Environmental Risk Factor Exposure to Failure to Thrive Functional disorder Gases Genes Goals Homeostasis Hospitalization Human Hyperplasia Hypoxemia Immune Impairment Individual Injections Investigation Knowledge Life Lung Lung diseases Modeling Molecular Morbidity - disease rate Mus Mutation Neuroendocrine Cell Neuroendocrine Therapy Neuroepithelial Bodies Neuropeptides Neurotransmitters Organ Other Genetics Output Oxygen Pathogenesis Pathologic Patients Pharmacological Treatment Pharmacology Phenotype Physiological Point Mutation Pulmonary Edema Rare Diseases Respiratory physiology Role Sampling Sensory Signal Transduction Stimulus Supportive care Symptoms Testing Translating Viral Respiratory Tract Infection Virus Diseases airway epithelium asthmatic attenuation cell type cohort constriction genetic approach in vivo infancy insight loss of function medical attention mouse model mutant non-invasive imaging pathogen pediatric patients pollutant prevent respiratory response sensor supplemental oxygen targeted treatment transcriptome sequencing

项目摘要

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.

项目概要婴儿神经内分泌细胞增生症（NEHI）是一种罕见的小儿肺部疾病，其特征是慢性呼吸急促、需要补充氧气的低血氧饱和度，并且常常无法生长。一个 NEHI 的病理特征是观察到肺中肺神经内分泌细胞的增加活检。然而，尚不清楚这种增加或其他遗传或环境因素是否导致了这种疾病。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患者突变的小鼠中。我们的初步数据表明该模型概括了关键特征的疾病。我们将使用该模型作为解决与 NEHI 相关的关键临床问题的切入点发病。由于除了支持性护理之外，没有针对 NEHI 的特殊疗法，我们的研究结果可能会提供信息针对 NEHI 疾病关键致病因素的特异性药物治疗。