UAB CFRC Core B: Animal and Preclinical Models Core

项目摘要/摘要 动物模型已经成为生物医学研究中越来越有价值的工具。动物模型是 尤其与对囊性纤维化(CF)的理解有关，在那里它们被广泛用于 鉴定CFTR的表达和功能，并探讨囊性纤维化的病理生理机制。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 支持大量涉及动物模型的P30研究人员的研究，以及创新的分析方法 可以用来描述它们的特征。 核心B履行具体目标中概述的三项主要职能。首先，核心B的品种、基因类型和 分发各种与CF相关的动物模型。它为数十个人提供了小鼠、大鼠、雪貂和猪的CF模型 当地、国家和国际P30调查人员。第二，核心帮助产生和采购 P30研究人员所要求的相关动物模型。核心帮助生成新的动物模型，使用 尖端重组技术，包括以UAB为中心的新型大鼠模型，以及最近的 该物种的人性化版本(被指定为国家核心资源)。此外，核心还获得了 P30研究人员需要的可用动物，如CF雪貂和猪模型。通过这种方式，核心 帮助研究人员开发和表征创新的动物模型，这些模型可以用来扩展当前的 CF研究的主体。第三，核心B制定了许多终点措施来评估CFTR功能， 慢性阻塞性肺疾病动物模型的上皮生理学、临床前终点和生物量分析。该端点 核心进行的分析包括：广泛的CFTR生理结果测量；上皮细胞的分析 功能；最先进的胃肠道和呼吸道成像方式(包括超声波、微型CT和 显微光学相干层析成像(第二个国家资源，见核心A)；生理分析，如 挠性肺功能、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。这些由Core B支持的尖端端点分析有助于揭示 疾病机制和途径，并阐明临床相关发现。 核心B提供了大量资源和技术专长，大大加强了P30调查人员的努力。 核心B提出的努力促进了思想交流和促进调查人员之间的合作。 此外，Core通过提供动物模型、电生理 设备、昂贵的成像设备、小动物支气管镜检查和组织/标本处理；以及 在许多调查人员之间共享的资源，而不需要在 多个实验室。在这些方面，P30核心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。

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.