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

• 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
• 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

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.

项目总结