COLLECTIN DEFICIENCY

描述(根据申请者的抽象和具体目标改编)： 使用SP-A和SP-D进行的大量不同实验的结果 (肺集合素)体外实验表明这两个相关蛋白参与了 至少有两个主要的生理过程：第一，肺的调节 表面活性物质动态平衡；第二，非特异性先天免疫反应 肺脏的。这个项目的总体目标是建立 植物体内SP-A和/或SP-D缺乏的生理后果 小鼠进一步了解完整动物体内的集合素功能 在健康和疾病方面。具体目标是：1)生成小鼠模型 肺集合素(SP-A和SP-D)缺乏症的连续基因研究 集合素基因座的破坏；2)表征肺力学和 表面活性物质的结构、功能及其在收集中的胞外代谢 缺陷小鼠a)在正常、非应激条件下，b)在运动期间， C)富含蛋白质的肺水肿和d)逆转 表面活性剂中磷脂酰甘油与磷脂酰肌醇(PG/PI)的比值 磷脂；以及3)确定肺集合素缺乏a)是否改变 对自发性呼吸道感染的易感性和b)增加 对甲型流感病毒感染易感性。

DESCRIPTION (Adapted from applicant's abstract and specific aims): The results from a large number of different experiments with SP-A and SP-D (lung collectins) in vitro suggest these two related proteins participate in at least two major physiologic processes: first, the regulation of lung surfactant homeostasis; and second, the non-specific innate immune response of the lung. The general objective of this project is to establish the physiological consequences of a deficiency in SP-A, SP-D or both proteins in mice to further our understanding of collectin function in the intact animal in health and disease. The specific aims are to: 1) generate mouse models of pulmonary collectin (SP-A and SP-D) deficiency by consecutive gene disruptions of the collectin locus; 2) characterize pulmonary mechanics and surfactant structure, function and extracellular metabolism in collectin deficient mice a) under normal, non-stressed conditions, b) during exercise, c) with protein-rich pulmonary edema and d) after reversing the phosphatidylglycerol to phosphatidylinositol (PG/PI) ratio in the surfactant phospholipids; and 3) determine if pulmonary collectin deficiency a) alters the susceptibility to spontaneous respiratory infection and b) increases the susceptibility to influenza A viral infection.