Genetics of complex behaviors in the mouse.

描述（由申请人提供）：本提案的长期目标是确定影响小鼠复杂行为的基因。我们选择对一个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，动物必须记住它周围的环境（或一个新的物体），这样它就可以在随后的接触这些环境时做出不同的反应。我们的特殊实验涉及到对开放领域的习惯。在这项任务中，老鼠被放置在一个开放的野外房间里，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，说明老鼠已经“习惯”了开阔的场地。因此，这个任务被认为是一个学习范例，因为它需要老鼠记住它以前在开放领域的经验。我们最近获得的初步数据表明，影响这一特性的一个（或多个）基因位于染色体（Chr）上。15的老鼠。在这项拨款申请中，我们现在想克隆这个基因，并研究它的特征和对行为的影响。

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.