Animal Models Core

核心C-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。尽管有几种疗法已经改善了 目前的治疗方法并不充分，而且CF仍然是一种致命的疾病。我们对此的了解 疾病的发病机制、进展和新生儿肺的状态是不充分的。这些差距存在于 我们的知识阻碍了开发更好的治疗和预防慢性肺病的尝试。一个 解决这些问题的主要障碍是动物模型的局限性。尽管小鼠品系 携带CFTR零和错义突变做出了巨大贡献，CF小鼠不会发展成 呼吸道或胰腺疾病，通常见于人类。我们已经产生了可以复制的CF型雪貂和猪 人类CF病的许多主要特征包括肠梗阻、胰腺外分泌破坏、 微小胆囊症，输精管畸形，局灶性胆汁性肝硬变，先天性呼吸道结构异常， 以及呼吸道和鼻窦感染随着时间的推移。动物模型核心的目标将是：(1)提供计划 调查人员与非CF和CF雪貂和猪进行了合作，以便他们能够成功地完成项目目标。(2) 建立新的基因工程的CF雪貂模型，以受监管的方式表达CFTR。(三)协助 实施小分子输送、从活体动物采集生物样本(例如， 对研究动物的护理和分析，以及对动物的护理和分析。 (四)协助项目备案，协调项目间动物使用情况。动物模型的核心 将通过已经建立的与项目负责人、病理学核心在体外的互动来无缝运作 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 由于这些人员为核心带来的承诺、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.