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.

项目摘要/摘要 动物模型已成为生物医学研究越来越有价值的工具。动物模型是 与对囊性纤维化（CF）的理解特别相关，在这些囊性纤维化（CF）中，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， 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 支持涉及动物模型的众多P30调查人员的研究，以及创新的测定 可用于表征它们。 核心B在特定目的中概述了三个主要功能。首先，核心B品种，基因型和 分发各种CF相关的动物模型。它为小鼠，大鼠，雪貂和猪提供CF模型 本地，国家和国际P30调查人员。其次，核心有助于一代和采购 P30研究人员需要的相关动物模型。核心有助于使用 最先进的重组技术，包括以UAB为中心的新型大鼠模型和最近 该物种的人性化版本（指定为国家核心资源）。此外，核心获得了 P30研究人员（例如CF雪貂和猪模型）所需的可用动物。这样，核心 帮助研究人员开发和表征可用于扩展当前的创新动物模型 CF研究机构。第三，核心B开发了许多终点测量来评估CFTR功能， CF动物模型中的上皮生理学，临床前终点和生物测量分析。端点 核心进行的测定包括：广泛的CFTR生理结局指标；上皮的测定 功能; GI和呼吸道的最先进的成像方式（包括超声，Micro-CT和 微光学相干断层扫描（第二个国家资源，请参见核心A）；生理测定，例如 屈曲肺功能，体积学和咳嗽监测；生存支气管镜检查；和技术 药物输送和监测。这些由核心B支持的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。 Core B提供了重要的资源和技术专长，从而大大增加了P30调查人员的努力。 核心B提出的努力促进了思想的分享并促进调查人员之间的合作。 此外，核心通过提供动物模型，电生理学来节省大量成本 设备，昂贵的成像方式，小动物支气管镜检查和组织/标本加工以及 在许多调查人员中共享的资源，而无需复制相同功能 多个实验室。通过这些方式，P30核心B对于研究优先级是必不可少的 总体UAB P30，包括研究CFTR细胞生物学，组织发病机理和临床翻译的研究。