Animal Models Core

核心C -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改善了 然而，由于患者的生命受到威胁，目前的治疗是不充分的，CF仍然是一种致命的疾病。我们的知识 该疾病的发病机制，其进展和新生儿肺的状态是不够的。这些差距在 我们的知识阻碍了开发CF肺病的更好治疗和预防的尝试。一 解决这些问题的主要障碍是动物模型的局限性。虽然小鼠品系 携带无效和错义CFTR突变的小鼠做出了巨大的贡献，CF小鼠不会发展出 呼吸道或胰腺疾病，通常见于人类。我们已经培育出CF雪貂和猪， 人CF疾病的许多关键特征包括肠梗阻，胰腺外分泌破坏， 微胆囊，输精管异常，局灶性胆汁性肝硬化，先天性气道结构异常， 以及气道和鼻窦感染。动物模型中心的目标是：（1）提供项目 研究人员与非CF和CF雪貂和猪，使他们能够成功地完成他们的项目目标。（二） 建立新的基因工程CF雪貂模型，以调控的方式表达CFTR。(3)协助 在进行小分子递送，从活动物中收获生物样品（例如， 支气管肺泡灌洗液、血液和微生物样品），以及研究动物的护理和分析。 (4)协助项目做好记录，协调项目间动物的使用。动物模型核心 将通过与项目负责人、病理学核心、体外 模型和细胞培养核心，以及管理核心。确保动物模型核心的成功 这是因为这些人给核心带来的承诺、经验和专业知识。

CORE C – 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. Although mouse strains carrying null and missense CFTR mutations have made enormous contributions, CF mice do not develop the airway or pancreatic disease typically found in humans. We have generated CF ferrets and 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: (1) To provide Program investigators with non-CF and CF ferrets and pigs so that they can successfully complete their project aims. (2) To build new genetically engineered CF ferret models that express CFTR in a regulated fashion. (3) To assist projects in carrying out small molecule delivery, the harvesting of biologic samples from live animals (e.g., bronchoalveolar lavage fluid, blood, and microbiological samples), and the care and analysis of study animals. (4) To assist projects in record keeping and coordinate animal usage among projects. The Animal Models Core will function seamlessly through already established interactions with the Project Leaders, Pathology Core, In Vitro Models and Cell Culture Core, and the Administrative Core. The success of the Animal Models Core is ensured because of the commitment, experience, and expertise that the personnel bring to the Core.