UAB CFRC Core B: Animal and Preclinical Models Core

UAB CFRC 核心 B：动物和临床前模型核心

• 批准号: 10673356
• 负责人: Susan Elizabeth Birket
• 金额: $ 28.5万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10673356
• 关键词: Acceleration; Animal Model; Animals; Area; Biological Assay; Biomedical Research; Breeding; Bronchoscopy; CRISPR/Cas technology; Cellular biology; Characteristics; Chronic; Cilia; Collaborations; Communities; Complement; Cost Savings; Coughing; Crossbreeding; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Defect; Disease; Drug Delivery Systems; Drug Monitoring; Electrophysiology (science); End Point Assay; Endocrine system; Epithelial Physiology; Epithelium; Equipment; Family suidae; Ferrets; Fostering; Functional disorder; Gastrointestinal tract structure; Gene Targeting; Generations; Genes; Genetic; Genetic Heterogeneity; Genome; Genotype; Glucose Intolerance; Goals; Image; International; Knock-out; Laboratories; Lung; Measurement; Measures; Mediating; Modeling; Monitor; Mouse Strains; Mucociliary Clearance; Mus; Mutation; Nose; Obstruction; Optical Coherence Tomography; Outcome Measure; Pancreas; Pathogenesis; Pathway interactions; Pharmacologic Substance; Phenotype; Physiological; Play; Plethysmography; Pre-Clinical Model; Predisposition; Property; Pseudomonas aeruginosa infection; Publications; Rattus; Recombinants; Research; Research Personnel; Research Priority; Research Support; Resource Sharing; Resources; Respiratory System; Role; Sample Size; Specimen Handling; Statistical Data Interpretation; Technical Expertise; Techniques; Technology; Tissue Sample; Tissues; Transgenic Organisms; Translations; X-Ray Computed Tomography; clinical predictors; clinical translation; clinically relevant; cystic fibrosis mouse; cystic fibrosis patients; effectiveness evaluation; epithelial Na+ channel; genetic manipulation; human disease; imaging modality; in vivo; innovation; interest; mRNA Decay; microCT; mouse model; mucus clearance; novel; novel therapeutics; porcine model; pre-clinical; promoter; pulmonary function; reproductive tract; tool; transcription activator-like effector nucleases; treatment response; ultra high resolution; ultrasound

Project Summary/Abstract Animal models have become an increasingly valuable tool for biomedical research. Animal models are particularly relevant to the understanding of cystic fibrosis (CF), where they are used extensively to characterize CFTR expression and function and investigate the pathophysiology of cystic fibrosis. Furthermore, animal models are critical to evaluating the effectiveness of novel therapies. The purpose of Core B is to support the research of numerous P30 investigators that involves animal models, and the innovative assays available to characterize them. Core B carries out three main functions as outlined in the Specific Aims. First, Core B breeds, genotypes, and distributes diverse CF relevant animal models. It provides CF models of mouse, rat, ferret and pig to dozens of local, national, and international P30 investigators. Second, the Core aids in the generation and procurement of relevant animal models required by P30 investigators. The Core helps generate new animal models using cutting edge recombinant technology, including the novel rat model centered at UAB and more recently humanized versions of this species (designated a National Core Resource). In addition, the Core acquires available animals needed by P30 investigators, such as the CF ferret and pig models. In this way, the Core helps investigators develop and characterize innovative animal models that can be used to expand the current body of CF research. Third, Core B has developed numerous endpoint measures to assess CFTR function, epithelial physiology, preclinical endpoints, and biospecimen analysis in CF animal models. The endpoint assays conducted by the core include: extensive CFTR physiological outcome measures; assays of epithelial function; state-of-the-art imaging modalities of the GI and respiratory tract (including ultrasound, micro-CT, and micro-optical coherence tomography (a second National Resource, see Core A); physiological assays such as Flexivent lung function, plethysmography, and cough monitoring; survival bronchoscopy; and techniques for drug delivery and monitoring. These cutting-edge endpoint analyses supported by Core B help to uncover disease mechanisms and pathways, and to elucidate clinically relevant findings. Core B provides significant resources and technical expertise that greatly augment efforts of P30 investigators. The efforts put forth by Core B foster the sharing of ideas and promote collaboration among investigators. Furthermore, the Core contributes to significant cost savings by providing animal models, electrophysiologic equipment, expensive imaging modalities, small animal bronchoscopy and tissue/specimen processing, and resources that are shared among many investigators without the need to duplicate the same capabilities in multiple laboratories. In these ways, P30 Core B is indispensable for the research priorities delineated by the overall UAB P30, including studies of CFTR cellular biology, tissue pathogenesis, and clinical translation.

项目总结/摘要 动物模型已成为生物医学研究中越来越有价值的工具。动物模型是 特别是与囊性纤维化（CF）的理解相关，它们被广泛用于 表征CFTR表达和功能，并研究囊性纤维化的病理生理学。此外，委员会认为， 动物模型对于评估新疗法的有效性至关重要。核心B的目的是 支持众多P30研究者的研究，包括动物模型和创新的检测方法。 可以用来描述它们。 核心B执行具体目标中概述的三个主要功能。首先，核心B品种、基因型和 分发各种CF相关动物模型。提供小鼠、大鼠、雪貂、猪CF模型， 当地、国家和国际P30研究者。第二，核心帮助生成和采购 P30研究者要求的相关动物模型。核心帮助产生新的动物模型， 尖端的重组技术，包括以UAB为中心的新型大鼠模型，以及最近 该物种的人源化版本（指定为国家核心资源）。此外，核心收购 P30研究者所需的可用动物，如CF雪貂和猪模型。这样，核心 帮助研究人员开发和表征创新的动物模型，可用于扩大电流 CF的研究。第三，核心B已经开发了许多终点指标来评估CFTR功能， CF动物模型中的上皮生理学、临床前终点和生物样本分析。端点 由核心进行的测定包括：广泛的CFTR生理结果测量;上皮细胞的测定; 功能;最先进的胃肠道和呼吸道成像模式（包括超声、微型CT和 显微光学相干断层扫描（第二个国家资源，见核心A）;生理测定，如 呼吸机肺功能、体积描记术和咳嗽监测;存活支气管镜检查; 药物输送和监测。核心B支持的这些尖端端点分析有助于发现 疾病机制和途径，并阐明临床相关的发现。 核心B提供了重要的资源和技术专长，极大地增强了P30调查人员的工作。 核心B所做的努力促进了研究人员之间的思想交流和合作。 此外，Core通过提供动物模型、电生理学模型、 设备、昂贵的成像模式、小动物支气管镜检查和组织/标本处理，以及 许多调查人员可以共享资源，而不需要重复相同的能力， 多个实验室。通过这些方式，P30 Core B对于由 总体UAB P30，包括CFTR细胞生物学，组织发病机制和临床翻译的研究。