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 项目概要 囊性纤维化（CF）是一种常见的常染色体隐性遗传疾病，由编码基因突变引起 囊性纤维化跨膜电导调节器（CFTR）。 CF 影响多个器官，包括肺、 胰腺、肠、肝脏、汗腺、胆囊和男性生殖道。呼吸道感染和 目前，炎症是导致大部分发病和死亡的原因。尽管多种疗法已经改善了 患者的生命，目前的治疗不足，CF 仍然是一种致命的疾病。我们对以下方面的了解 该疾病的发病机制、进展以及新生儿肺部的状态尚不明确。这些差距 我们的知识阻碍了开发更好的治疗和预防 CF 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 携带无效和错义 CFTR 突变做出了巨大贡献，CF 小鼠没有发展出 通常在人类中发现的气道或胰腺疾病。我们已经培育出了能够复制的 CF 雪貂和猪 人类 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、 随着时间的推移，气道和鼻窦也会发生感染。动物模型核心的目标是： (1) 提供程序 研究人员使用非 CF 和 CF 雪貂和猪，以便他们能够成功完成他们的项目目标。 (2) 建立新的基因工程 CF 雪貂模型，以受监管的方式表达 CFTR。 (3) 协助 进行小分子递送、从活体动物（例如， 支气管肺泡灌洗液、血液和微生物样本），以及研究动物的护理和分析。 (4) 协助项目保存记录并协调项目之间的动物使用。动物模型核心 将通过与项目负责人、病理学核心、体外建立的互动无缝运作 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 因为这些人员为核心带来的承诺、经验和专业知识。