TRANSGENIC MOUSE MODEL FOR SICKLE ACUTE CHEST SYNDROME

镰状急性胸部综合症转基因小鼠模型

• 批准号: 2596295
• 负责人: Lewis Li-Yen Hsu
• 金额: $ 8.2万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-10 至 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2596295
• 关键词: cell adhesion; disease /disorder model; genetically modified animals; hydroxyurea; laboratory mouse; lung injury; monocyte; neutrophil; nonhuman therapy evaluation; pathologic process; sickle cell anemia

DESCRIPTION (Adapted from applicants' abstract) Overall objectives: Develop an animal model for the sickle acute chest syndrome (ACS), a life-threatening complication of human sickle cell disease, in order to study pathophysiology and test therapy. The applicant, who is trained in pediatric hematology-oncology, proposes to learn methods in pulmonary research and endothelial cell adhesion research under the mentorship of a pulmonologist and a hematologist. The study hypothesis is that pathophysiology of ACS includes erythrocyte (RBC) sickling and adhesion, neutrophils, and monocytes. Mice will be used to examine the effects of hydroxyurea, which has shown therapeutic benefit in preventing ACS, in relation to RBC and leukocytes. Using the murine models of sickle cell disease currently available to the applicant, plethysmographic measures of pulmonary function will complement the histopathologic studies of structure. The applicant will extend the studies as collaborations make other mice available during the course of the project. The Georgia-NIH Comprehensive Sickle Cell Center (co-sponsor James Eckman), the Lung Biology Group in Atlanta VA Medical Center (co-sponsor Samuel Aguayo), active groups in endothelial cell adhesions at Georgia Institute of Technology and Emory University, and microcirculation group at the Morehouse School of Medicine. Hypothesis: Transgenic mice expressing human sickle hemoglobin are more susceptible than normal mice to acute lung injury from oleic acid injection, due to abnormal interactions of blood cells and endothelium. Specific aims are to examine the roles of different blood cells in increased susceptibility to acute lung injury. 1. Abnormal RBC - (a) sickling, (b) adhesion; 2. Neutrophils - (a) numbers, (b) adhesion/retention, (c) activation; 3. Monocytes - (a) numbers, (b) adhesion/retention, (c) activation; 4. Examine effects hydroxyurea on RBC, neutrophils, and monocytes in acute lung injury. (End of Abstract)

描述 （改编自申请人的摘要）总体目标：发展动物 镰状急性胸部综合征（ACS）的模型，一种威胁生命的 为了研究病理生理学的人类镰状细胞疾病的并发症 和测试疗法。 申请人接受了小儿培训 血液学肿瘤学提议学习肺部研究中的方法 肺科医生的指导下的内皮细胞粘附研究 和血液学家。 研究假设是ACS的病理生理学 包括红细胞（RBC）寒败和粘附，中性粒细胞和 单核细胞。 小鼠将用于检查羟基脲的作用，该羟基脲 在预防ACS方面显示了与RBC相关的ACS的治疗益处 白细胞。 使用目前镰状细胞疾病的鼠模型 可用于申请人，肺功能的成分测量值 将补充结构的组织病理学研究。 申请人 随着协作使其他老鼠在期间可用时，将扩展研究 项目的过程。 佐治亚州立大学综合镰状细胞中心 （共同赞助者詹姆斯·埃克曼 中心（共同赞助者Samuel Aguayo），内皮细胞中的活跃组 佐治亚理工学院和埃默里大学的粘连， Morehouse医学院的微循环小组。 假设： 表达人类镰刀血红蛋白的转基因小鼠比 正常小鼠因异常而导致油酸急性肺损伤 血细胞和内皮的相互作用。 具体目的是检查 不同血细胞在增加急性肺的敏感性中的作用 受伤。 1。异常的RBC - （a）病，（b）粘附； 2。中性粒细胞 - （a）数字，（b）粘附/保留，（c）激活； 3。单核细胞 - （a） 数字，（b）粘附/保留率，（c）激活； 4。检查效果 RBC上的羟基脲，中性粒细胞和急性肺损伤中的单核细胞。 （结尾 抽象）