Core 1: Animal and Cell Model Core

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 向项目调查人员提供模型，并协调和标准化模型的共享使用。集成 ACM核心是病理学子核心，它将处理动物组织以满足 个别项目。将在具有饮食诱导的肥胖的KC小鼠中研究肥胖对PDAC的影响 (DIO)或遗传诱导的肥胖，这将允许区分饮食的直接肿瘤促进作用， 真正的肥胖效应。对于DIO模型，将动物随机分配至对照组 饮食或高脂肪、高热量饮食（HFCD），并评估对肿瘤发展的影响。从基因上来说- 在诱导的肥胖模型中，KC小鼠将被杂交到瘦素缺陷型ob/ob背景（KCO）中。的ACM 核心将与所有三个项目合作进行主要的干预性研究，其中KC小鼠被 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 除了主要的动物研究，ACM核心将进行项目特定的干预，并将回交 将KC模型转化为额外的遗传背景。核心的主要目标是：1）提供动物- 为所有项目提供相关服务和新型细胞培养模型，2）最大限度地减少重复劳动并降低成本 通过协调实验（共享动物和组织使用），以及3）减少由不同的 确保动物处理和数据收集的一致性（集中 资源和专业知识）。ACM Core为每个项目提供的服务包括： 保持机构批准，在后勤和统计能力方面设计动物研究 计算（与项目PI和生物统计子核心一起），保持动物品系和设置 育种对，所有动物的基因分型，动物随机分配至实验组，制备和 实验饮食或干预的施用，日常监测和动物护理，动物的安乐死， 在处死时收获组织和血液，处理组织，例如固定在福尔马林中并包埋在石蜡中，以及 切片（连同病理学子核心）、组织切片的组织病理学评价（连同 病理学子核心），原代细胞培养物（PanIN和鼠胰腺癌）的产生， 鼠和人胰腺类器官培养物、原始数据的储存、组织和生物学的中央库 样本，组织分配到各个项目，与项目负责人讨论结果，以及培训 动物手术的项目研究者（如需要）。

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).