CORE--BEHAVIORAL SCREENING

核心——行为筛查

• 批准号: 6108383
• 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: 1999
• 资助国家: 美国
• 起止时间: 1999-01-01 至 1999-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6108383
• 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，开发，以满足需要的行为和 Core C产生小鼠新突变体的组织学筛选 1、2、3、5、6、7号项目建议书。具有识别的 几个基因可能涉及神经和行为表型的 DS，该项目建议生产基因操纵小鼠， 确定单个基因或基因区域在表型中的作用 的DS。这些模型将包括a）节段性三体小鼠; B）转基因小鼠 小鼠; c）敲除小鼠; d）Cre-Lox复制和缺失，以及e） a和b-d之间的交叉。因为许多这样的基因 操纵小鼠将被创建（估计每年6只），因为 在大多数情况下，那些产生老鼠的人没有接受过行为训练， 分析，核心设施是必要的，以筛选所有突变体的神经 和行为表型。用于产生突变小鼠的努力 将被浪费，除非有用的表型可以通过系统检测， 分析.这一核心将采用双重战略。一是各 动物将在固定筛选组合中进行试验。的目标 电池对广泛的行为效应敏感， 特别是在DS小鼠模型中预测的那些，并且基于 经过验证的筛选电池。其次，在预测是 如果可能的话，测试将被设计成进入行为领域， 预计会受到影响。具有生产性表型的小鼠将被 进一步追求的神经生物学和行为水平， 个别项目或将提供给其他研究人员。的 基本电池将评估反射，筛查异常行为，评估 感觉和运动功能、情绪、活动、习惯化、疼痛 敏感性和依赖性学习。质量控制 将实施程序，以确保 行为测试，以及遗传和环境背景的 突变体将被仔细控制，以提供有效的结论， 从这个核心产生的数据中提取。附加服务包括 开发和维护规范行为数据库 Rod博士对所有新小鼠的背景品系和组织学进行了研究， 布朗森核心将由琳达克尼克博士担任，她有20多个 年评估啮齿动物模型的经验， 全职技术员