Animal Model Resources for Cystic Fibrosis

描述（由申请人提供）：囊性纤维化（CF）是一种复杂的全身性和致死性疾病，涉及气道功能受损、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，包括来自感染的改变的炎症特征、内分泌干扰、代谢异常、青春期延迟和不育、肠梗阻、肠和气道杯状细胞增生、改变的上皮生物电特性等，因此提供了许多与人类疾病相关的表型，但因此需要特殊的饲养。因此，我们当地的CF Animal Core已成为CF和CF相关小鼠的国际分销商，程序培训设施以及分析和小鼠组织样本资源。我们的CF相关小鼠的种类继续增长，正如需求一样，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要求它们的研究人员。此外，我们建议提供CF小鼠器官和组织的组织库，沿着年龄和性别匹配的对照品，可应要求提供给研究者。最后，我们还建议对CF和非CF小鼠的匹配组织进行转录组学和蛋白质组学分析，并将这些数据提供给研究人员用于假设生成和/或测试。 该提案利用了我们使用CF小鼠的历史和规模经济，这对于较小的殖民地来说是不可能的。CF Animal Core是十多年前设计的，旨在为我们CF中心的研究人员产生CF动物，但已经发展得远远超出了这一点，为世界各地的研究人员提供CF小鼠，双转基因和我们最近产生的条件等位基因。需求继续增加，因此，我们在此建议提供额外资源，以满足我们自己的需要以及其他寻求与CF有关的问题的人的需要。为了实现这些目标，具体目标是：1）产生CF疾病修饰物的鼠模型以在体内研究修饰物机制，2）产生表达人CFTR及其致病突变体的CF小鼠模型以用于CFTR校正的研究或需要体内环境的其他CFTR研究，3）提供在统一条件（年龄、性别、饮食等）下收集的CF和对照小鼠器官库。和4）从CF小鼠组织产生转录组和蛋白质组数据库用于假设产生。

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.