Nutrition/Animal Core/Kevin Fritsche

营养/动物核心/Kevin Fritsche

• 批准号: 8007177
• 负责人: DENNIS B LUBAHN
• 金额: $ 9.52万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8007177
• 关键词: Analytical Chemistry; Animal Feed; Animal Model; Animal Nutrition; Animals; Astrocytes; Botanicals; Breeding; Cell physiology; Chemicals; Development; Diet; Disease; Dose; Drug Formulations; Energy Intake; Folk Medicine; Gene Deletion; Gene Expression; Generations; Genotype; Goals; Guidelines; Health; Human; Immune response; Intake; Life; Malignant neoplasm of prostate; Mediating; Mind; Mouse Strains; Mus; Nutrient; Outcome; Phagocytes; Prostate; Quality Control; Reperfusion Injury; Research; Research Design; Research Project Grants; Rodent; Role; Screening procedure; Signal Pathway; Techniques; Testing; Time; Tissues; Translating; Virus Diseases; Work; base; cost; dosage; feeding; human NOS2A protein; mouse model; novel; nutrition; pre-clinical

This Core has two primary objectives: (1) to formulate and produce all experimental diets required for animal feeding trials to be conducted within the Center; (2) to produce, through breeding, mice of novel genotypes required for the studies designed to test hypotheses relating to underlying mechanism for the actions of botanicals. Experimental diets will be formulated according to the most recent guidelines such that the quantity and quality of the nutrients provided is both appropriate and consistent throughout the life of the Center. Botanicals and bioactive components will be incorporated into experimental diets in amounts that follow principles of allometric scaling and the concept of hormesis. The goal being to test mice at levels of botanicals that will readily translate into human intake/exposure levels. This core will work closely with the Analytical Chemistry Core to conduct quality control analyses on all diets to assure consistency from batchto- batch. This Center will generate nearly 6,000 mice per year to investigate the bioactivity and possible modes of action for the botanicals under study. The impact of botanicals on prostate cancer development will be explored in TRAMP mice, a well-characterized mouse model for this disease. Initial studies in Projects #2 & #3 will use some common strains of mice (e.g., C57BI/6) to investigate the impact of botanicals on ischemia-reperfusion injury and host response to bacterial and viral infection, respectively. The role of key signaling pathways for the actions of botanicals will be investigated by using tissue-specific gene deletion techniques (i.e., Cre-flox expression targeting) in all three projects. The role of Nrf2-dependent gene expression in botanical-mediated changes in cell function and health outcomes will be explored using mice with astrocyte-, phagocyte-, and prostate-specific deletions of Keapl. Additional mice with neuronaland astrocyte-specific deletions of N0X2, INOS, and nNOS will be generated to support testing novel hypothesis for Project #2 as research findings dictate.

该核心有两个主要目标：（1）制定和生产动物所需的所有实验饲料 在中心内进行饲养试验;（2）通过育种生产新基因型小鼠 为检验与药物作用的基本机制有关的假设而设计的研究所需的资料。 植物药实验饮食将根据最新的指南配制， 提供的营养素的数量和质量在整个生命周期内都是适当和一致的。 中心植物和生物活性成分将被纳入实验饮食的数量， 遵循异速生长比例原则和毒物兴奋效应概念。目标是测试小鼠的水平 植物性药物，很容易转化为人类摄入/暴露水平。这一核心将与 分析化学核心对所有饲料进行质量控制分析，以确保从批次到批次的一致性。 批次该中心每年将产生近6,000只小鼠，以研究生物活性和可能的 所研究植物药的作用方式。植物对前列腺癌发展的影响 将在TRAMP小鼠中探索，TRAMP小鼠是这种疾病的良好表征的小鼠模型。初步研究 项目#2和#3将使用一些常见的小鼠品系（例如，C57 BI/6），以研究植物性药物的影响 对缺血再灌注损伤和宿主对细菌和病毒感染的反应。的作用 植物药作用的关键信号通路将通过使用组织特异性基因进行研究 删除技术（即，Cre-flox表达靶向）。Nrf 2依赖的作用 植物介导的细胞功能和健康结果变化中的基因表达将使用 星形胶质细胞、吞噬细胞和前列腺特异性缺失Keapl的小鼠。额外的neuronaland小鼠 将产生N 0X 2、INOS和nNOS的星形胶质细胞特异性缺失，以支持检测新的 研究结果表明，项目#2的假设。