Genetic Dissection of a Motor Central Pattern Generator

以及重复的随意肌肉运动，如搅拌或舔液体。啮齿动物的液体舔是一种 一个有希望的、简单的CPG模型的例子：这是一种高度刻板的行为，其特征是 有节奏的舌头和下巴运动，被认为是由分布在体内的一种神经底物控制的 脑干中的延髓网状结构。在初步观察中，我们已经证明 菌株C57BL/6J(B6)和DBA/2J(D2)在舔食率方面有很强的、不重叠的表型差异。 识别导致舔舌率差异的基因应该会为研究人类免疫缺陷病毒 CPGS。然后，小鼠可以通过基因靶向的删除或插入来创造，从而允许特定的生理或 解剖学研究。我们建议利用一种新增加的资源来研究我们的基因 这些鼠标将允许 对构成行为特征的数量性状基因座(QTL)进行精确的遗传定位。我们建议使用 一种用于检测一组-80株BXD RL菌株的新型高通量舔舌率方法，并定位了数量性状基因座 (QTL)具有高精度，这是舔舌率的应变变化的基础。 相关性：复杂的动物，如人类，具有许多刻板印象的运动反应 和/或本质上重复的。刻板印象重复的基因和机制的比较 运动与塑形行为将成为与许多人类CMS相关的信息来源 涉及反常重复运动的紊乱。

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 vs. plastic behaviors will be a source of information relevant for a number of human CMS disorders involving abnormal repetitive movements.