CORE--BEHAVIORAL SCREENING

核心——行为筛查

• 批准号: 6301896
• 负责人: Linda S. Crnic
• 金额: $ 17.74万
• 依托单位: ELEANOR ROOSEVELT INST FOR CANCER RES
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-01-01 至 2000-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6301896
• 关键词: Downs syndrome; animal developmental psychology; behavior prediction; behavior test; behavioral /social science research tag; biomedical facility; chromosome 21; computer assisted sequence analysis; gene deletion mutation; gene targeting; genetic manipulation; genetically modified animals; histopathology; laboratory mouse; longitudinal animal study; mutant; neuroanatomy; neurobiology; neuropsychology; phenotype; tissue /cell preparation; trisomy

This is a new core that was developed to meet the need for behavioral and histological screening of new mouse mutants produced by Core C for project 1,2,3,5,6 and 7 of this program of projects proposal. Having identified several genes potentially involved in the neural and behavior phenotype of DS, the projects proposed to produce genetically manipulated mice to determine the roles of individual genes or gene regions in the phenotype of DS. These models will include a) segmental trisomic mice; b) transgenic mice; c) knock-out mice d) Cre-Lox duplications and deletions and e) crosses between a and b-d. Because a number of such genetically manipulated mice will be created (an estimated six per year) and because those generating the mice are in most case not trained in behavioral analysis, a core facility is necessary to screen all mutants for neural and behavioral phenotype. The effort applied to generating mutant mice will be wasted unless useful phenotypes can be detected by systematic analysis. A two-fold strategy will be used for this core. First, all animals will be tested on a fixed screening battery. The goal of the battery is to be sensitive to a wide range of behavioral effects, particularly those predicted in a mouse model of DS, and is based on validated screening batteries. Second, in cases where prediction is possible, tests will be designed to tap into the behavioral domains that are expected to be affected. Mice with productive phenotypes will be further pursued as the neurobiological and behavioral level in the individual projects or will be made available to other investigators. The basic battery will assess reflexes, screen for abnormal behaviors, assess sensory and motor function, emotionality, activity, habituation, pain sensitivity and hippocampally-dependent learning. Quality control procedures will be implemented to ensure reliability and consistency in behavioral testing, and the genetic and environmental backgrounds of the mutants will be carefully controlled to provide valid conclusions to be drawn from the data generated by this core. Additional services include the development and maintenance of a database of normative behavior data on the background strains used, and histology on all new mice by Dr. Rod Bronson. The core will be staffed by Dr. Linda Crnic, who has over 20 years experience assessing rodent models of mental retardation, and a full-time technician.

这是一个新的核心，它被开发来满足行为和 用于项目的Core C产生的新小鼠突变体的组织学筛选 本项目建议书方案1、2、3、5、6、7。在确定了 几个可能与脑瘫的神经和行为表型有关的基因 DS，这些项目建议生产基因操纵的小鼠来 确定单个基因或基因区域在表型中的作用 DS中的。这些模型将包括a)节段性三体小鼠；b)转基因 小鼠；c)基因敲除小鼠d)Cre-Lox复制和缺失以及e) A和b-d之间的交叉点。因为许多这样的基因 被操纵的小鼠将被创造出来(估计每年有6只)，因为 在大多数情况下，产生老鼠的人没有接受过行为方面的培训 分析，一个核心设施是筛选所有神经突变体所必需的 和行为表型。用于培育突变小鼠的努力 除非系统检测到有用的表型，否则将被浪费 分析。这一核心将采用双重战略。首先，所有 动物将在固定的筛查电池上进行测试。的目标是 电池对广泛的行为影响很敏感， 尤其是在DS的小鼠模型中预测的那些，并基于 经过验证的屏蔽电池。第二，在预测是 有可能，测试将被设计成进入行为领域， 预计都会受到影响。具有多产表型的小鼠将是 作为神经生物学和行为水平的进一步追求 个别项目或将提供给其他调查人员。这个 基本电池将评估反射、筛选异常行为、评估 感觉和运动功能、情绪性、活动量、习惯性、疼痛 敏感性和海马体依赖学习。质量控制 将实施程序，以确保可靠性和一致性 行为测试，以及基因和环境背景 变种人将受到仔细控制，以提供有效的结论 从这个核心产生的数据中提取。其他服务包括 规范行为数据库的开发与维护 罗德博士在所有新小鼠上使用的背景菌株和组织学 布朗森。核心将由Linda Crnic博士担任工作人员，她有20多个 多年评估智力低下啮齿动物模型的经验，以及 全职技术员。