Animal Model Resources for Cystic Fibrosis

囊性纤维化动物模型资源

• 批准号: 8688376
• 负责人: Mitchell L Drumm
• 金额: $ 50.48万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8688376
• 关键词: Age; Alleles; Animal Model; Animals; Area; Biological Assay; Communities; Complex; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Data; Databases; Delayed Puberty; Diabetic Diet; Diet; Disease; Endocrine; Endocrine disruption; Epithelial; Gene Expression Profile; Generations; Goals; Human; Immune System Diseases; Immunology; Infection; Infertility; Inflammatory; International; Intestinal Obstruction; Intestines; Investigation; Metabolic; Modeling; Molecular Profiling; Monoclonal Antibody R24; Mus; Organ; Phenotype; Physiology; Procedures; Property; Proteome; Proteomics; Recording of previous events; Research; Research Infrastructure; Research Personnel; Resources; Testing; Tissue Banking; Tissue Banks; Tissue Sample; Tissues; Training; Transgenic Organisms; Work; airway goblet cell hyperplasia; cystic fibrosis mouse; design; human disease; in vivo; interest; mRNA Expression; mouse model; mutant; novel; programs; protein expression; sex; trait; transcriptomics

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.

描述（由申请人提供）：囊性纤维化（CF）是一种复杂的、全身性和致命性疾病，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，包括感染引起的炎症谱改变、内分泌紊乱、代谢异常、青春期延迟和不育、肠梗阻、肠道和气道杯状细胞增生、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，但因此需要特殊的饲养。因此，我们当地的CF Animal Core已经成为CF和CF相关小鼠的国际经销商，一个程序培训设施，以及化验和小鼠组织样本的资源。我们与cf相关的小鼠种类继续增长，需求也在增长，在这里，我们建议扩大我们的动物群体的范围，使它们可用于我们自己的研究项目，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，以及年龄和性别匹配的对照，可应要求提供给研究人员。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。