Genetic and environmental determinants of neuro-behavioural development in genetically modified mice

转基因小鼠神经行为发育的遗传和环境决定因素

• 批准号: 7441-2013
• 负责人: Brown, Richard
• 金额: $ 3.42万
• 依托单位: Dalhousie University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2013
• 资助国家: 加拿大
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=521009
• 关键词: Genetic; environmental; determinants; neuro; behavioural

We will use inbred and genetically modified mice to study basic questions about the relationships between genes, the environment, brain and behaviour. Three series of experiments will be done to (1) define multiple memory systems (2) analyze lifespan developmental psychobiology and (3) solve methodological problems in the study of mouse behavioural phenotyping. Why it is important? We know very little about the gross effects of genetic manipulation on the behavioural phenotypes of mice. This research uses an ethological and a multiple memory systems approach to understand the effects of genetic manipulation and environmental effects on cognitive function. Only when we understand the wide-ranging effects of genetic manipulation on behavioural phenotypes will we be able to understand how genes influence behaviour. These research projects aim to define the neuro-behavioural changes in genetically modified mice, and relate these changes to strain differences in genes, their patterns of expression, and their effect on neural and behavioural changes throughout the lifespan. What are the anticipated outcomes? We will define the changes in the behavioural phenotypes of inbred and transgenic mice across their lifespan, and describe the genetic, epigenetic, neural, immune and endocrine mechanisms underlying these lifetime changes in behavioural phenotype and define the optimal research protocols for determining the lifespan psychobiological changes in these behavioural phenotypes. What is the benefit to the field and to Canada? There is currently a great deal of confusion about the effects of genes on behaviour. This research will determine the optimal methodology for studying cognitive function in genetically altered mice and show the wide-ranging effects of gene manipulation on behavioural phenotypes and their underlying neurobiological process throughout development. It will also show how environmental experiences interact with gene expression in behavioural development. Finally, it will help us to understand how gene mutations can result in enhanced and abnormal behavioural development.

我们将使用近亲繁殖和转基因小鼠来研究关于基因、环境、大脑和行为之间关系的基本问题。将进行三个系列的实验：(1)定义多重记忆系统；(2)分析寿命发育心理生物学；(3)解决小鼠行为表型研究中的方法学问题。为什么它很重要？我们对基因操作对小鼠行为表型的总体影响知之甚少。这项研究使用行为学和多记忆系统的方法来理解遗传操作和环境效应对认知功能的影响。只有当我们了解基因操作对行为表型的广泛影响时，我们才能理解基因是如何影响行为的。这些研究项目旨在定义转基因小鼠的神经行为变化，并将这些变化与基因的品系差异、它们的表达模式以及它们在整个生命周期中对神经和行为变化的影响联系起来。预期的结果是什么？我们将定义近交系和转基因小鼠一生中行为表型的变化，描述这些行为表型变化背后的遗传、表观遗传、神经、免疫和内分泌机制，并定义确定这些行为表型的寿命心理生物学变化的最佳研究方案。这对田野和加拿大有什么好处？目前，人们对基因对行为的影响有很大的困惑。这项研究将确定研究转基因小鼠认知功能的最佳方法，并展示基因操作对行为表型及其整个发育过程中潜在的神经生物学过程的广泛影响。它还将展示环境体验如何与行为发展中的基因表达相互作用。最后，它将帮助我们理解基因突变如何导致增强和异常的行为发育。