Tissue and neurobehavioral phenotyping core

组织和神经行为表型核心

• 批准号: 10417058
• 负责人: KAREN M RIDGE
• 金额: $ 29.9万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10417058
• 关键词: Aging; Alveolar; Animal Model; Attention; Biological Assay; Blinded; Brain; Breeding; Cells; Disease; Enterobacteria phage P1 Cre recombinase; Environment; Equilibrium; Exploratory Behavior; Flow Cytometry; Funding Opportunities; Generations; Genes; Genetically Engineered Mouse; Genotype; Human Resources; Immune; Inflammatory; Influenza A virus; Injury; Instruction; Intervention; Knock-out; Knockout Mice; Learning; Liquid substance; LoxP-flanked allele; Lung; Magnetic Resonance Imaging; Mass Spectrum Analysis; Measurement; Measures; Mechanics; Memory; Modeling; Monitor; Motor; Motor Activity; Mus; Muscle; Muscle function; Nociception; Outcome Measure; Pathway interactions; Phenotype; Pneumonia; Population; Program Research Project Grants; Protocols documentation; Pulmonary Inflammation; Reaction; Reproducibility; Research; Research Personnel; Resources; Response Latencies; Rotarod Performance Test; Running; Skeletal Muscle; Sorting - Cell Movement; Standardization; Techniques; Testing; Tissues; Travel; Virus Diseases; age related; aged; behavior test; cell type; cost; cytokine; experience; falls; indexing; influenza A pneumonia; influenza infection; injury and repair; interest; knockout animal; lung injury; lung repair; mouse model; neurobehavioral; novel; object recognition; programs; proteostasis; recruit; skeletal; synergism; tool; transcriptomics

PROJECT SUMMARY The Tissue and Neurobehavioral Phenotyping Core, designated as Core C, is a centralized facility that will provide investigators with a well-established and reproducible model of influenza A–induced pneumonia. Quantitative tools such as Flexivent measurements of lung mechanics, magnetic resonance imaging to evaluate lung repair and remodeling, and multiplex measures of pro-inflammatory cytokines will be conducted by Core C according to the research plan outlined in Projects 1, 2, and 3. Core C will use advanced flow cytometry capabilities to quantify, phenotype, and sort specific inflammatory and parenchymal cell populations from the murine lung, brain, and muscle. The sorting and isolation capabilities of the Core will allow cell-type- specific assessment of proteostasis networks via mass spectroscopy (as outlined by Core B). Core C will breed mice to generate the cell-type- or tissue-specific Cre recombinase lines to induce tissue-specific knockout mice. Core C will perform the genotyping of all the murine strains proposed by Project Leaders. Core C will maintain a uniform environment in which wild-type and genetically engineered mice will be aged. Importantly, Core C will assess the impact of influenza A–induced pneumonia on age-related changes in neurobehavioral phenotypes. Briefly, Core C will examine motor coordination and balance by means of an accelerating rotarod test. Response latency on a hot plate will be tested to assess nociceptive functions. Exploratory behaviors and locomotor activity will be examined in an open field assay and by continuous monitoring with running wheels. Learning and memory will be examined in novel object recognition and Barnes maze tests. Collectively, these tools provide a unique resource for Project Investigators, which would be difficult to reproduce without the support of this PPG.

项目摘要 组织和神经行为表型核心，指定为核心C，是一个集中的设施，将 为研究者提供了一个完善的和可重复的甲型流感诱导的肺炎模型。 定量工具，如肺力学的快速测量，磁共振成像， 评估肺修复和重塑，并进行促炎细胞因子的多重测量 根据项目1、2和3中概述的研究计划，由核心C完成。核心C将使用高级流 定量、表型和分类特定炎症和实质细胞群的细胞计数能力 从小鼠的肺、脑和肌肉中提取。核心的分类和分离能力将允许细胞类型- 通过质谱法对蛋白质稳态网络进行特异性评估（如核心B所述）。核心C将 繁殖小鼠以产生细胞类型或组织特异性Cre重组酶系，以诱导组织特异性 敲除小鼠核心C将对项目负责人提出的所有鼠品系进行基因分型。核心 C将维持一个统一的环境，野生型和基因工程小鼠将在其中老化。 重要的是，核心C将评估甲型流感诱导的肺炎对年龄相关变化的影响， 神经行为表型简单地说，核心C将检查运动协调和平衡的手段， 加速转棒试验将测试热板上的反应潜伏期以评估伤害感受功能。 探索行为和自发活动将在旷场试验中进行检查，并通过连续 用转轮进行监测。学习和记忆将在新的物体识别和巴恩斯检查 迷宫测试总的来说，这些工具为项目调查人员提供了一个独特的资源， 如果没有PPG的支持，很难复制。