Genetics of rest:activity behavior in the mouse

休息遗传学：小鼠的活动行为

• 批准号: 6616233
• 负责人: MAJA BUCAN
• 金额: $ 34.12万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6616233
• 关键词: behavior test; behavioral /social science research tag; behavioral genetics; body physical activity; circadian rhythms; electrodes; electroencephalography; electromyography; electrophysiology; gene expression; gene mutation; genetic mapping; genetic markers; genetic polymorphism; genetic regulation; genotype; in situ hybridization; laboratory mouse; linkage mapping; microarray technology; molecular cloning; neurobiology; rest; sleep; sleep disorders; wakefulness

DESCRIPTION (provided by applicant): The long term goal of our studies is to identify genetic factors that underlie molecular events involved in the regulation of rest:activity behavior in the mouse. We employed forward genetics approach to identify single gene mutations that cause gross changes in activity levels or organization of rest:activity cycles. These changes may be due to general metabolic or developmental defects, or caused by anomalies in neurobiological processes, such as the circadian system and regulation of sleep. We have established an integrated and nested phenotypic protocol, which will allow us to characterize novel mutations on several levels; molecular, neuropathological, electrophysiological and behavioral. Our aims are: Aim 1) Genetic characterization, mapping and positional cloning of rest/activity mutants, identified by random ENU (N-ethyl-N-nitrosourea) mutagenesis; 1) Aim 2) Characterization of sleep patterns in selected rest:activity mutants; Aim 3) Determination of the specificity of rest:activity disturbances; Aim 4) Microarray analysis will be used to define downstream pathways disrupted by the mutant gene. Initially, this project includes genetic and phenotypic characterization of two mutations, one with an effect on circadian period (Rooster), and second, Bedlam, associated with a decreased amplitude of the circadian rhythms. Our hypothesis is that a subset of rest:activity mutations will uncover novel genes involved in the regulation of sleep and their interaction with the other neurobiological processes, such as those that underlie learning and memory or circadian system. Human orthologs of loci defined by these single gene mutations may represent additive or interactive contributions to the polygenic component of inherited psychiatric and sleep disorders.

描述（由申请人提供）：我们研究的长期目标是确定参与调节小鼠休息：活动行为的分子事件背后的遗传因素。我们采用正向遗传学方法来识别导致活动水平或休息组织（活动周期）发生总体变化的单基因突变。这些变化可能是由于一般代谢或发育缺陷造成的，也可能是由神经生物学过程的异常引起的，例如昼夜节律系统和睡眠调节。我们已经建立了一个集成的嵌套表型方案，这将使我们能够在多个层面上表征新的突变；分子、神经病理学、电生理学和行为学。我们的目标是： 目标 1) 通过随机 ENU（N-乙基-N-亚硝基脲）诱变鉴定的休息/活性突变体的遗传表征、作图和位置克隆； 1) 目标 2) 表征选定的休息：活动突变体的睡眠模式；目标 3) 确定休息的特异性：活动障碍；目标 4) 微阵列分析将用于确定被突变基因破坏的下游途径。最初，该项目包括两种突变的遗传和表型特征，一种突变影响昼夜节律（公鸡），第二种突变与昼夜节律振幅降低相关。 我们的假设是，休息：活动突变的一个子集将揭示参与睡眠调节及其与其他神经生物学过程相互作用的新基因，例如那些构成学习和记忆或昼夜节律系统基础的神经生物学过程。由这些单基因突变定义的人类基因座直系同源物可能代表对遗传性精神疾病和睡眠障碍的多基因成分的附加或相互作用的贡献。