Animal Model Resources for Cystic Fibrosis

囊性纤维化动物模型资源

• 批准号: 8181444
• 负责人: Mitchell L Drumm
• 金额: $ 56.04万
• 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 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8181444
• 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. PUBLIC HEALTH RELEVANCE (provided by applicant): Animal models are crucial for understanding mechanisms of human disease as well as for developing and testing potential therapies. The project outlined in this application accelerates the availability of cystic fibrosis mouse models, their tissues, mRNA expression and protein expression profiles to investigators interested in CF-related questions.

描述（由申请人提供）：囊性纤维化（CF）是一种复杂，全身性和致命性疾病，涉及气道功能受损，内分泌和代谢破坏，免疫功能障碍以及许多其他特征。 CF小鼠概括了人类疾病的大多数疾病特征，包括感染，内分泌干扰，代谢异常，青春期和不育症的延迟，肠道障碍，肠道和气道go骨细胞增生，需要改变的上皮生物电子疾病的人类和许多相关性的现象型的炎症，肠道和气道细胞增生，肠道go虫的增生，肠道梗阻，肠道梗阻，肠道梗阻，肠道障碍和不育，肠道障碍，肠道障碍和不育细胞增生，肠道障碍和不育细胞增生改变了许多现象。结果，我们本地的CF动物核心已成为CF和CF相关小鼠的国际分销商，一种程序的训练设施以及用于测定和小鼠组织样品的资源。我们的各种与CF相关的小鼠的各种需求一样，我们在这里建议扩大殖民地中动物的范围，并使它们适合我们自己的研究计划以及任何要求它们的调查人员。此外，我们建议根据要求提供一组CF小鼠器官和组织的组织库以及年龄和性别匹配的对照。最后，我们还建议对来自CF和非CF小鼠匹配的组织进行转录组和蛋白质组学分析，并将这些数据用于研究人员，以进行假设产生和/或测试。 该提案利用了CF小鼠的历史，而对于较小的殖民地来说，不可能实现规模经济。该提案进化的CF动物核心是十年前设计的，目的是为我们的CF中心的研究人员生成CF动物，但已经远远超出了此类研究，为CF小鼠提供了CF小鼠，双转基因以及我们最近产生的条件等位基因，并向世界各地的研究者提供了。需求继续增加，因此我们在这里建议提供更多资源，以适应我们自己的需求以及其他提出与CF相关问题的人的需求。 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从CF小鼠组织产生转录组和蛋白质组数据库，以产生假设的产生。 公共卫生相关性（由申请人提供）：动物模型对于理解人类疾病的机制以及开发和测试潜在疗法至关重要。在此应用中概述的项目加速了囊性纤维化小鼠模型的可用性，其组织，mRNA表达和蛋白质表达谱，并向对与CF相关问题感兴趣的研究者。