Core A: Animals Models-Stoltz

核心A -动物模型 项目摘要 囊性纤维化（CF）是一种常见的常染色体隐性遗传病，由编码 囊性纤维化跨膜传导调节因子（CFTR）。CF影响多个器官，包括肺， 胰腺、肠、肝、汗腺、胆囊和男性生殖道。呼吸道感染和 炎症目前引起大部分的发病率和死亡率。虽然有几种疗法已经有所改善 然而，由于CF严重威胁患者的生命，目前的治疗是不充分的，并且CF仍然是致命的疾病。我们的知识 关于疾病的发病机制，其进展，以及新生儿肺的状态是不够的。 这些知识上的差距阻碍了我们为CF开发更好的治疗和预防方法的尝试 肺病。解决这些问题的主要障碍是动物模型的局限性。我们 产生的CF猪复制了人类CF疾病的许多关键特征， 梗阻，胰腺外分泌破坏，微胆囊，输精管异常，局灶性胆道 肝硬化、先天性气道结构异常和气道和鼻窦感染。的目标 动物模型核心将是（1）：为项目研究者提供非CF和CF猪，以便他们能够 成功完成项目目标;（2）建立新的基因工程CF猪模型;（3）协助 从活体动物中采集生物样品的项目（例如，支气管肺泡灌洗液和血液）， 研究动物的护理和分析，记录保存，并协调项目之间的动物使用。的 动物模型核心将通过与项目负责人已经建立的互动无缝运作 和核心董事。动物模型核心的成功是因为承诺， 经验和专业知识的人员带来的核心。

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.