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.