Core 1: Animal and Cell Model Core

核心1：动物和细胞模型核心

• 批准号: 10605252
• 负责人: Guido Erwin Michael Eibl
• 金额: $ 28.57万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10605252
• 关键词: Animal Euthanasia; Animal Model; Animals; Area; Backcrossings; Biological; Biometry; Blood; Breeding; Calories; Cell Culture Techniques; Cell model; Chemoprevention; Collaborations; Comprehensive Cancer Center; Data; Data Collection; Development; Diet; Dietary Component; Digestive System Disorders; Drug or chemical Tissue Distribution; Ensure; Environment; Evaluation; Fatty acid glycerol esters; Flow Cytometry; Formalin; Generations; Genetic; Genetically Engineered Mouse; Genotype; Human; Human Resources; Individual; Institution; Intervention; Intervention Studies; KRASG12D; Laboratories; Laboratory Research; Leptin deficiency; Logistics; Malignant neoplasm of pancreas; Medical center; Modeling; Monitor; Mus; Obesity; Organoids; Pancreas; Pancreatic Adenocarcinoma; Pancreatic Diseases; Pancreatic Intraepithelial Neoplasia; Paraffin; Pathology; Phase; Preparation; Primary Cell Cultures; Procedures; Process; Random Allocation; Randomized; Research Personnel; Resource Sharing; Resources; Sampling; Sampling Studies; Services; Standardization; Tissue Banks; Tissue Harvesting; Tissues; Tumor Promotion; Work; animal care; animal facility; animal imaging; animal tissue; cost; design; diet-induced obesity; dietary control; experimental group; experimental study; innovation; member; mouse model; novel; pancreatic cancer model; programs; square foot; three dimensional cell culture; tissue processing; training project; tumor

PROJECT SUMMARY The main objective of the Animal and Cell Model (ACM) Core is to provide animal and innovative cell culture models to the Project investigators and to coordinate and standardize the shared use of the models. Integrated into the ACM Core is the Pathology Sub-Core, which will process animal tissues to meet the needs for the individual projects. The impact of obesity on PDAC will be investigated in KC mice with diet-induced obesity (DIO) or genetically-induced obesity, which will allow to distinguish direct tumor promoting effects of dietary components from true obesity effects. For the DIO model, animals will be randomly allocated to either a control diet or a high fat, high calorie diet (HFCD) and the effect on tumor development assessed. For the genetically- induced obesity model, KC mice will be crossed into the leptin deficient ob/ob background (KCO). The ACM Core will carry out in collaboration with all three projects the main interventional study, in which KC mice are treated with statins. Tissues from this large study will be shared among and analyzed by all three projects. In addition to the main animal study, the ACM Core will conduct Project-specific interventions and will back-cross the KC model into additional genetic backgrounds. The main objectives of the Core are 1) to provide animal- related services and novel cell culture models to all Projects, 2) to minimize duplication of effort and reduce costs by coordinating experiments (shared animal and tissue use), and 3) to reduce variability introduced by different environments and husbandry and to ensure consistency in animal handling and data collection (concentration of resources and expertise). Services that the ACM Core provides for each Project include: obtaining and maintaining institutional approval, designing the animal studies in terms of logistics and statistical power calculations (together with Project PI's and Biostatistics Sub-Core), maintaining animal strains and setting up breeding pairs, genotyping of all animals, randomization of animals to experimental groups, preparation and administration of experimental diets or interventions, daily monitoring and animal care, euthanasia of animals, harvest of tissues and blood at sacrifice, processing tissue, e.g. fixing in formalin and embedding in paraffin, and sectioning (together with the Pathology Sub-Core), histopathological evaluation of tissue sections (together with the Pathology Sub-Core), generation of primary cell cultures (PanINs and murine pancreatic cancer), generating the murine and human pancreatic organoid cultures, storage of raw data, central banking of tissues and biological samples, distribution of tissues to individual Projects, discussion of results with Project Leaders, and training of Project investigators in animal procedures (if desired).

项目摘要 动物和细胞模型（ACM）核心的主要目标是提供动物和创新的细胞培养 向项目调查人员进行模型，并协调和标准化模型的共同使用。融合的 进入ACM核心的是病理亚核，该病理将处理动物组织以满足对 个别项目。肥胖对PDAC的影响将在饮食引起的肥胖症的KC小鼠中研究 （DIO）或遗传诱导的肥胖症，这将允许区分饮食的直接肿瘤作用 来自真实肥胖作用的成分。对于DIO模型，动物将被随机分配给对照 饮食或高脂肪，高热量饮食（HFCD）以及评估对肿瘤发育的影响。对于遗传 诱导的肥胖模型，KC小鼠将被跨入瘦素缺乏OB/OB背景（KCO）。 ACM 核心将与所有三个项目合作进行主要介入研究，其中KC小鼠是 用他汀类药物治疗。这项大型研究的组织将在所有三个项目中共享和分析。在 除了主要动物研究外，ACM核心将进行特定项目的干预措施，并将反向交叉 KC模型成为其他遗传背景。核心的主要目标是1）提供动物 - 所有项目的相关服务和新颖的细胞培养模型，2）最大程度地减少努力的重复并降低成本 通过协调实验（共享动物和组织使用），以及3）减少不同的变异性 环境和饲养，并确保动物处理和数据收集的一致性（集中度 资源和专业知识）。 ACM核心为每个项目提供的服务包括：获取和 维持机构批准，根据物流和统计能力设计动物研究 计算（与Project Pi和Biostatistics子核一起），保持动物菌株并设置 繁殖对，所有动物的基因分型，动物与实验组的随机化，制备和 给予实验饮食或干预措施，日常监测和动物护理，动物安乐死， 牺牲时组织和血液的收获，加工组织，例如固定福尔马林并嵌入石蜡，以及 切片（与病理亚核），组织切片的组织病理学评估（一起） 病理亚核），原代细胞培养物（Panins和Murine Pancreatic Cancer）的产生 鼠类和人类胰器官培养物，原始数据的存储，组织和生物学 样本，组织分配到各个项目，与项目负责人的结果讨论以及培训 项目调查人员在动物程序中（如果需要）。