Core A: Animals Models-Stoltz

核心A-动物模型 项目总结 囊性纤维化是一种常见的常染色体隐性遗传病，由编码 囊性纤维化跨膜电导调节剂(CFTR)。Cf影响多个器官，包括肺部， 胰腺、肠道、肝脏、汗腺、胆囊腺和男性生殖道。呼吸道感染和 目前，炎症是导致大多数发病率和死亡率的原因。尽管有几种治疗方法已经有所改善 尽管目前的治疗方法不足以挽救患者的生命，但它仍然是一种致命的疾病。我们的知识 关于该病的发病机制、进展，以及新生儿肺的状态尚不充分。 我们知识上的这些差距阻碍了开发更好的治疗和预防CF的尝试 肺部疾病。解决这些问题的一个主要障碍是动物模型的局限性。我们 产生的CF猪复制了包括肠道在内的许多人类CF疾病的关键特征 梗阻、胰腺外分泌破坏、微小胆囊症、输精管异常、胆管局灶性病变 肝硬化、先天性呼吸道结构异常，以及随时间推移的呼吸道和鼻窦感染。世界银行的目标是 动物模型的核心将是(1)：为项目调查人员提供非CF和CF猪，以便他们能够 成功完成项目目标；(2)构建新的转基因CF猪模型；(3)协助 从活体动物采集生物样本(例如，支气管肺泡灌洗液和血液)的项目； 研究动物的护理和分析，记录和协调项目间的动物使用。这个 动物模型核心将通过已经建立的与项目负责人的互动来无缝运行 和核心董事。动物模型核心的成功是因为承诺， 这些人员为核心带来的经验和专业知识。

CORE A – ANIMAL MODELS PROJECT SUMMARY Cystic fibrosis (CF) is a common autosomal recessive disease caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). CF affects multiple organs, including lungs, pancreas, intestine, liver, sweat glands, gallbladder and the male genital tract. Airway infection and inflammation currently cause most of the morbidity and mortality. Although several therapies have improved the lives of patients, current treatments are inadequate and CF remains a lethal disease. Our knowledge about the pathogenesis of the disease, its progression, and the state of the neonatal lung is inadequate. These gaps in our knowledge have hindered attempts to develop better treatments and preventions for CF lung disease. A major impediment to addressing these issues had been limitations of animal models. We generated CF pigs that replicate many of the key features of human CF disease including intestinal obstruction, exocrine pancreatic destruction, micro-gallbladder, vas deferens abnormalities, focal biliary cirrhosis, congenital airway structural abnormalities, and airway and sinus infection with time. The goals of the Animal Models Core will be to (1): Provide Program investigators with non-CF and CF pigs so that they can successfully complete their project aims; (2) Build new genetically engineered CF pig models; (3) Assist projects in the harvesting of biologic samples from live animals (e.g., bronchoalveolar lavage fluid and blood), the care and analysis of study animals, record keeping, and coordinate animal usage among projects. The Animal Models Core will function seamlessly through already established interactions with the Project Leaders and Core Directors. The success of the Animal Models Core is ensured because of the commitment, experience, and expertise that the personnel bring to the Core.