Genetic Dissection of a Motor Central Pattern Generator

运动中枢模式发生器的基因剖析

• 批准号: 7207470
• 负责人: John D Boughter
• 金额: $ 12.78万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-01-15 至 2008-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7207470
• 关键词: Animals; Appointment; Behavior; Behavioral; Biological Neural Networks; Brain Stem; Candidate Disease Gene; Chromosome Mapping; Complex; Data; Disease; Dissection; Gene Targeting; Genes; Genetic; Genotype; Health Sciences; Human; Inbred Strain; Inbred Strains Mice; Investigation; Knowledge; Lead; Liquid substance; Location; Maps; Measures; Modeling; Molecular; Motor; Movement; Mus; Nature; Numbers; Physiological; Plastics; Quantitative Trait Loci; Rate; Rattus; Recombinants; Resources; Reticular Formation; Rodent; Single Nucleotide Polymorphism; Skeletal Muscle; Source; Stereotyped Behavior; Stereotyping; Tennessee; Testing; Thinking; Tongue; Universities; Variant; base; central pattern generator; density; genetic resource; high throughput screening; insight; interest; jaw movement; novel; progenitor; relating to nervous system; response; trait

DESCRIPTION (provided by applicant): Central pattern generators (CPGs) are rhythmically active neural networks that underlie many stereotyped and repetitive voluntary muscle movements such as whisking or fluid licking. Fluid licking in rodents is an example of a promising, simple model of a CPG: It is a highly stereotyped behavior characterized by rhythmic tongue and jaw movements, and it is thought to be controlled by a neural substrate distributed in the medullary reticular formation in the brainstem. In preliminary observations, we have demonstrated that mice are a superb species choice for investigating the genetic basis of the licking CPG - the common inbred strains C57BL/6J (B6) and DBA/2J (D2) have a robust, non-overlapping phenotypic difference in lick rate. The identification of genes underlying differences in lick rate should have a huge payout for the study of CPGs. Mice can then created with gene-targeted deletions or insertions, allowing for specific physiological or anatomical investigation. We propose to take advantage of a newly augmented resource for our genetic dissection of licking: The BXD advanced recombinant inbred (Rl) strain set. These mice will allow for precision genetic mapping of quantitative trait loci (QTL) that underlie behavioral traits. We propose to use a novel high-throughput assay for lick rate to test a set of -80 BXD Rl strains, and map quantitative trait loci (QTLs) with high precision that underlie strain variation in lick rate. Relevance: Complex animals such as humans possess a number of motor responses that are stereotypic and/or repetitive in nature. Comparison of the genes and mechanisms underlying stereotyped repetitive movements versus plastic behaviors will be a source of information relevant for a number of human CMS disorders involving abnormal repetitive movements.

描述（由申请人提供）：中枢模式发生器（CPG）是有节奏的活动神经网络，是许多刻板和重复的自愿肌肉运动（如搅拌或液体舔）的基础。啮齿类动物的液体舔是CPG的一个有前途的简单模型的例子：它是一种高度刻板的行为，其特征是有节奏的舌头和下颌运动，并且被认为是由分布在脑干中的髓质网状结构中的神经基质控制的。在初步观察中，我们已经证明小鼠是研究舔CPG遗传基础的极好物种选择-常见的近交系C57 BL/6 J（B6）和DBA/2 J（D2）在舔率方面具有稳健的、非重叠的表型差异。识别舔食率差异的潜在基因对CPG的研究应该有巨大的回报。然后可以用基因靶向缺失或插入来创建小鼠，从而允许进行特定的生理或解剖学研究。我们建议利用一个新增加的资源，我们的遗传解剖舔：BXD先进的重组近交系（RI）菌株集。这些小鼠将允许精确的遗传作图的数量性状基因座（QTL）的基础行为特征。我们建议使用一种新的高通量测定舔率的方法来测试一组约80个BXD Rl菌株，并以高精度定位舔率菌株变异的数量性状基因座（QTL）。相关性：复杂的动物，如人类，拥有许多固有的和/或重复的运动反应。定型重复运动与塑性行为的基因和机制的比较，将是一个信息的来源，涉及异常重复运动的一些人类CMS疾病相关。