Animal Model Resources for Cystic Fibrosis

描述(申请人提供)：囊性纤维化(CF)是一种复杂的、全身性和致命性疾病，涉及呼吸道功能受损、内分泌和代谢紊乱、免疫功能障碍和许多其他特征。CF小鼠概括了人类疾病的大部分疾病特征，包括感染引起的炎症特征改变、内分泌中断、代谢异常、青春期延迟和不孕、肠梗阻、肠道和呼吸道杯状细胞增生、上皮生物电特性改变等，因此提供了许多与人类疾病相关的表型，但因此需要特殊饲养。因此，我们当地的CF Animal Core已经成为CF及其相关小鼠的国际分销商、程序培训设施以及检测和小鼠组织样本的资源。随着需求的增长，我们与CF相关的小鼠的种类也在继续增长，在这里，我们建议扩大我们殖民地的动物范围，并使它们可用于我们自己的研究计划，以及任何提出要求的研究人员。此外，我们建议提供一个组织库，包括CF小鼠器官和组织，以及年龄和性别匹配的对照，可供研究人员根据要求使用。最后，我们还建议对CF和非CF小鼠的匹配组织进行转录和蛋白质组学分析，并将这些数据提供给研究人员用于假设生成和/或测试。 这项提议利用了我们与CF小鼠的历史和规模经济，这对较小的殖民地来说是不可能的。十多年前，我们为我们的CF中心的研究人员设计了CF动物核心，以产生CF动物核心，但已经进化得很久，为世界各地的研究人员提供了CF小鼠、双转基因和最近产生的条件性等位基因。需求继续增加，因此，我们建议在此提供更多资源，以满足我们自己以及其他寻求与气候变化有关问题的人的需要。为了实现这些目标，具体的目标是：1)建立CFR疾病修饰剂的小鼠模型，以研究活体内的修饰机制；2)建立表达人CFTR及其致病突变体的CF小鼠模型，用于CFTR校正的研究或其他需要体内环境的CFTR研究；3)提供CF库并控制在统一条件下(年龄、性别、饮食等)收集的小鼠器官。4)从CF小鼠组织中建立转录组和蛋白质组数据库，用于假设生成。

DESCRIPTION (provided by applicant): Cystic fibrosis (CF) is a complex, systemic and lethal disorder, involving impaired airway function, endocrine and metabolic disruption, immune dysfunction, and many other traits. The CF mouse recapitulates most of the disease features of the human disorder, including an altered inflammatory profile from infection, endocrine disruption, metabolic anomalies, delayed puberty and infertility, intestinal obstruction, intestinal and airway goblet cell hyperplasia, altered epithelial bioelectric properties, etc., and thus provides numerous phenotypes relevant to the human disease, but consequently requires special husbandry. As a consequence, our local CF Animal Core has become an international distributor of CF and CF-related mice, a training facility for procedures and a resource for assays and mouse tissue samples. Our assortment of CF-related mice continues to grow, as does demand, and here we propose to expand the scope of animals in our colony and to make them available for our own research programs as well as to any investigators requesting them. Additionally, we propose to provide a tissue bank of CF mouse organs and tissues, along with age and sex-matched controls, available to investigators upon request. Lastly, we also propose to carry out transcriptomic and proteomic analyses on matched tissues from CF and non-CF mice and to make these data available to investigators for hypothesis generation and/or testing. The proposal capitalizes on our history with CF mice and an economy of scale not possible for smaller colonies. The CF Animal Core from which this proposal evolved was designed over a decade ago to generate CF animals for investigators at our CF Center, but has evolved well beyond that, providing CF mice, double transgenics, and most recently conditional alleles that we have generated, to investigators around the world. Demand continues to increase, and thus we propose here to provide additional resources that accommodate our own needs as well as those of others pursuing questions related to CF. To accomplish these goals, the specific aims are: 1) to produce murine models of CF disease modifiers to study modifier mechanisms in vivo, 2) to create CF mouse models expressing human CFTR and its disease- causing mutants for studies of CFTR correction or other CFTR studies requiring in vivo contexts, 3) to provide a bank of CF and control mouse organs collected under uniform conditions (age, sex, diet, etc.) and 4) to generate transcriptome and proteome databases from CF mouse tissues for hypothesis generation.