Genetics of complex behaviors in the mouse.

小鼠复杂行为的遗传学。

基本信息

批准号：
7196432
负责人：
VALERIE J BOLIVAR
金额：
$ 31.28万
依托单位：
WADSWORTH CENTER
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-03-01 至 2010-02-28
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): The long term goal of this proposal is to identify the gene(s) that influence complex behavior in the mouse. We have chosen habituation to an open field as our first behavior to be analyzed. Habituation is a form of memory whereby an animal must remember its surroundings (or a novel object) such that it can respond differently on its subsequent exposure to these surroundings. Our particular assay involves habituation to an open field. In this task, mice are placed in an open field chamber and their activity is recorded on three consecutive days. If their activity changes over the three days, the mice have "habituated" to the open field. This task is therefore considered a learning paradigm since it requires the mouse to remember its previous experience in the open field. We have recently obtained preliminary data indicating that a gene (or genes) influencing this trait resides on Chromosome (Chr.) 15 of the mouse. In this grant application, we would now like to clone this gene as well as study its characteristics and effects on behavior. Our specific aims are as follows: (1) to produce B6.D2 and D2.B6 speed congenics and subcongenics for regions of Chr. 15 in the mouse. These strains will be used to further map this habituation trait as well as provide useful strains for further behavioral studies; (2) to test Chr. 15 congenics and subcongenics for behavioral traits including habituation. A battery of tests will be used to determine if performance in the habituation task correlates with performances on other tasks. Alcohol and drug-related behaviors will also be screened; (3) to identify candidate genes for the genetic control of habituation. Candidate genes will be identified either by examining polymorphic differences between strains or by comparing differences in gene expression in target tissues; and (4) to confirm the identity of candidate genes by making transgenic mice. Three strategies will be considered--(1) BAC transgenesis with BACs containing candidate genes, (2) knockin mice containing regions of known polymorphisms in candidate genes or (3) knockout mice and complementation studies that will reveal the hemizygous influence of the candidate gene. These genetically engineered mice will be used to explore the in vivo effects of the detected polymorphisms. It is anticipated that the successful positional cloning of this gene will lead to new information on the pathways involved in the habituation process.

描述（由申请人提供）：该提案的长期目标是确定影响小鼠复杂行为的基因。我们选择对开放领域的习惯作为我们要分析的第一个行为。习惯化是一种记忆形式，动物必须记住其周围环境（或新物体），以便在随后暴露于这些环境时能够做出不同的反应。我们的特殊测定涉及对开放场地的习惯。在这项任务中，小鼠被放置在露天室中，并连续三天记录它们的活动。如果它们的活动在三天内发生变化，则小鼠已经“习惯”了开阔的场地。因此，这项任务被认为是一种学习范例，因为它要求小鼠记住其先前在开放领域的经验。我们最近获得的初步数据表明，影响该性状的一个或多个基因位于小鼠的 15 号染色体上。在这项拨款申请中，我们现在想要克隆该基因并研究其特征和对行为的影响。我们的具体目标如下： (1) 为 Chr. 区域生产 B6.D2 和 D2.B6 速度同类基因和亚同类基因。 15 在鼠标中。这些菌株将用于进一步绘制这种习惯特征，并为进一步的行为研究提供有用的菌株； (2) 测试 Chr。行为特征（包括习惯）的 15 个同类和亚同类。将使用一系列测试来确定习惯任务中的表现是否与其他任务中的表现相关。酒精和毒品相关行为也将受到筛查； (3)鉴定遗传控制习惯化的候选基因。将通过检查菌株之间的多态性差异或通过比较目标组织中基因表达的差异来鉴定候选基因； (4)通过制作转基因小鼠来确认候选基因的身份。将考虑三种策略——(1) 使用含有候选基因的 BAC 进行 BAC 转基因，(2) 含有候选基因已知多态性区域的敲入小鼠，或 (3) 敲除小鼠和互补研究，以揭示候选基因的半合子影响。这些基因工程小鼠将用于探索检测到的多态性的体内效应。预计该基因的成功定位克隆将带来有关习惯化过程所涉及途径的新信息。