Animal Models Core

动物模型核心

• 批准号: 10024664
• 负责人: DAVID A STOLTZ
• 金额: $ 61.06万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10024664
• 关键词: Address; Affect; Airway Disease; Animal Model; Animals; Biliary cirrhosis; Biological; Blood; Bronchoalveolar Lavage Fluid; Caring; Cell Culture Techniques; Consultations; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Disease; Disease Progression; Ensure; Exocrine pancreas; Family suidae; Ferrets; Gallbladder; Genes; Genetic Engineering; Goals; Harvest; Human; Human Resources; Infection; Inflammation; Intestinal Obstruction; Intestines; Knowledge; Liver; Lung; Male Genital Organs; Measures; Microbiology; Modeling; Molecular; Monitor; Morbidity - disease rate; Mouse Strains; Mutation; Neonatal; Organ; Pancreas; Pancreatic Diseases; Pathogenesis; Pathology; Patients; Prevention; Production; Program Research Project Grants; Pulmonary Cystic Fibrosis; Research Personnel; Sampling; Sinus; Structural defect; Sweat Glands; Time; Vas deferens structure; animal care; cystic fibrosis mouse; disease-causing mutation; experience; health assessment; improved; in vitro Model; mortality; programs; reproductive tract; sample collection; small molecule; success

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.

核心C - 动物模型 项目摘要 囊性纤维化（CF）是由编码基因突变引起的常见常染色体隐性疾病 囊性纤维化跨膜电导调节剂（CFTR）。 CF影响包括肺在内的多个器官 胰腺，肠，肝脏，汗腺，胆囊和雄性生殖道。气道感染和 目前，炎症会导致大部分发病率和死亡率。尽管几种疗法改善了 患者的生活，目前的治疗不足，CF仍然是致命的疾病。我们对 疾病的发病机理，其进展和新生儿肺的状态不足。这些差距 我们的知识阻碍了为CF肺部疾病开发更好的治疗方法和预防措施的尝试。一个 解决这些问题的主要障碍是动物模型的局限性。虽然小鼠菌株 携带无效和错义CFTR突变已做出了巨大的贡献，CF小鼠不会发展 在人类中通常发现的气道或胰腺疾病。我们产生了复制的CF雪貂和猪 人类CF疾病的许多关键特征，包括肠反应，外分泌胰腺破坏， 微型加仑，VAS延期异常，局灶性胆道肝硬化，先天性气道结构异常， 随着时间的流逝，气道和鼻窦感染。动物模型核心的目标将是：（1）提供程序 非CF和CF雪貂和猪的研究人员可以成功完成项目的目标。 （2） 建立新的一般工程的CF雪貂模型，以受管制的方式表达CFTR。 （3）协助 进行小分子递送的项目，从活体动物中收集生物样品（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）协助项目在项目之间进行记录和协调动物使用情况。动物模型核心 通过已经建立的与项目领导者，病理核心，体外建立的互动，将无缝发挥作用 模型和细胞培养核心以及行政核心。确保动物模型核心的成功 由于人事带来的承诺，经验和专业知识。