Animal Core

动物核心将为所有四个项目提供主要的动物模型(条件性Kras‘^鼠模型)。 杂合子LSL-Kras小鼠将与杂合子PDX-1-Cre小鼠杂交。后代将会是 用小鼠尾巴聚合酶链式反应检测Kras突变等位基因和Cre转基因 DNA突变小鼠(LSL-Kras；Pdx-1-Cre)将被随机分配给对照组(AIN-76A)。 或者高脂肪、高卡路里饮食(HFCD)。然后，每个试验组将被分配到 个别项目特定的治疗和灌输/强化。动物核心将开展与以下各方面相关的活动 该项目特定的动物研究。在3、6、9和12个月或 根据机构指导方针提前终止。在祭祀时，组织，包括整个 胰腺、其他器官和血液将被采集和处理。准确的后处理程序 取决于个别项目的要求和需要。一般来说，一半的胰腺会被固定在 福尔马林和石蜡包埋(用于标准组织学和免疫组织化学)，另一半冷冻 在液氮中(用于RNA和蛋白质分析)。一小块胰腺将被用于基因分型 (以检测成功的重组事件)。包括在动物核心中的是病理学分核心， 这将为所有小鼠骨骼的组织病理学评价提供依据。动物核心组织提供的服务 为每个项目提供的资金包括：获得和维护机构批准，设计动物 在逻辑和统计能力计算方面的研究(与PI项目和生物统计学一起 次核心)，维持动物品系和建立繁殖对，对所有动物进行基因分型， 将动物随机分成试验组，制备和给药试验性饲料或 灌输、日常监测和动物护理、动物安乐死、组织和血液采集。 牺牲、处理组织，例如用福尔马林固定和石蜡包埋，以及切开(连同 病理分项)、组织切片的组织病理学评估(与病理分项一起 核心)、细胞培养(Panlns和小鼠胰腺癌)的生成、原始数据的存储、中央 保存问题和生物样本，将问题分配给个别项目，讨论结果 与项目负责人一起，对项目调查人员进行动物程序方面的培训(如果需要)。 相关性(请参阅说明)： 动物核心的目标是最大限度地减少重复工作并通过协调 由不同的项目调查人员进行的实验，以便动物和组织可以由 调查人员，如果可能的话。通过集中，动物研究所需的资源将 利用效率非常高(与单独进行动物研究的单个项目相比)。 提供集中的动物服务将确保动物处理和数据收集的一致性。

The Animal Core will provide the main animal model (conditional Kras'^^^^ mouse model) to all four projects. Heterozygous LSL-Kras'^^^¿^* mice will be crossed with heterozygous Pdx-1-Cre mice. Offspring will be genotyped for the presence of the mutated Kras allele and Cre transgene using PCR analysis of mouse tail DNA. Mutant mice {LSL-Kras¿^^¿'^;Pdx-1-Cre) will be randomly allocated to either the control diet (AIN-76A) or the high fat, high calorie diet (HFCD). Each of the experimental groups will then be allocated to the individual project-specific treatments and inten/enfions. The Animal Core will conduct all aspects related to the Project-specific animal studies. Cohorts of mice will be sacrificed at 3, 6, 9, and 12 months or prematurely terminated according to the institutional guidelines. At sacrifice, tissues, including the entire pancreas, other organs and blood will be harvested and processed. The exact post-processing procedures depend on the individual Project requirements and needs. In general, half of the pancreas will be fixed in formalin and embedded in paraffin (for standard histology and immunohistochemistry), the other half frozen in liquid nitrogen (for RNA and protein analysis). A small piece of the pancreas will be used for genotyping (to detect the successful recombination event). Included in the Animal Core is the Pathology Sub-Core, which will provide the histo-pathological evaluafion of all mouse fissues. Services that the Animal Core provides for each Project include: Obtaining and maintaining institutional approval, designing the animal studies in terms of logisfics 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 inten/entions, 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 secfioning (together with the Pathology Sub-Core), histopathological evaluation of tissue sections (together with the Pathology Sub- Core), generation of cell cultures (PanlNs and murine pancreafic cancer), storage of raw data, central banking of fissues and biological samples, distribufion of fissues to individual Projects, discussion of results with Project Leaders, training of Project investigators in animal procedures (if desired). RELEVANCE (See instructions): The Animal Core's objecfives are to minimize duplication of effort and reduce costs by coordinating the experiments performed by different Project Investigators so that animals and tissues may be shared by the investigators, where possible. Through the centralization, resources needed for the animal studies will be utilized very efficiently (as compared to the individual Projects performing their animal studies separately). Providing centralized animal services will ensure consistency in animal handling and data collection.