Genetics of Taste Perception

描述（由申请人提供）：味觉是决定食物或饮料是否被摄入或拒绝的主要感官系统。味道也会影响消化系统对食物的处理。因此，了解这种感觉背后的机制对我们控制营养摄入和调节可能导致肥胖、高血压和代谢综合征等疾病的过度消耗的能力至关重要。我们推进对味觉感知的理解的方法是使用小鼠模型来识别参与感知的基因。我们首先在近亲繁殖的小鼠品系中识别出味觉刺激行为反应的自然变异，然后利用这些信息来定位和识别导致这种变异的基因。这种方法，有时被称为定位克隆，能够检测涉及味觉感知各个阶段的基因，从味蕾细胞的接收到负责味觉刺激行为反应的大脑功能。在我们之前的研究中，我们首次成功地使用位置克隆技术来鉴定与哺乳动物行为有关的功能基因，我们鉴定并表征了一个编码甜味受体的基因座。在目前的综合建议中，我们描述了旨在继续识别参与对甜化合物的行为反应的基因的研究。我们还建议扩大研究范围，包括与酸味有关的基因。这种定位克隆方法将与个体基因作用的生理机制的行为分析相辅相成。这些研究完成后，可能为旨在改变过度食物消费的干预措施提供重要的新途径。味觉是决定一种食物或饮料是否会被摄入或拒绝的主要感觉系统。因此，了解这种感觉背后的机制对我们控制营养摄入和调节可能导致肥胖、高血压和代谢综合征等疾病的过度消耗的能力至关重要。我们以小鼠为模型生物研究味觉机制。我们的方法，有时被称为位置克隆，是基于负责味觉反应变异的基因的染色体定位。在此之前，我们用这种方法确定了一个编码甜味受体的基因座。在目前的综合建议中，我们描述了旨在继续识别与甜味有关的基因的研究。我们还建议扩大我们的范围，包括酸味相关的基因。这些研究完成后，可能为旨在改变过度食物消费的干预措施提供重要的新途径。

DESCRIPTION (provided by applicant): The sense of taste is the primary sensory system that determines whether a food or beverage will be ingested or rejected. Taste also influences food processing by the digestive system. Consequently, understanding the mechanisms underlying this sense is central to our ability to control intake of nutrients and to modulate the excesses of consumption that may underlie diseases such as obesity, hypertension and the metabolic syndrome. Our approach to advancing understanding of taste perception has been to use mouse models to identify genes involved in perception. We first identify natural variation in behavioral responses to taste stimuli in inbred mouse strains and then use this information to locate and identify the genes responsible for this variation. This approach, sometimes called positional cloning, is capable of detecting genes involved in all stages of taste perception, from reception in taste bud cells to brain functions responsible for behavioral responses to taste stimuli. In our previous studies, which were the first successful use of positional cloning to identify a functional gene involved in mammalian behavior, we identified and characterized a locus that codes for a sweet taste receptor. In the current comprehensive proposal, we describe studies designed to continue to identify genes involved in behavioral responses to sweet compounds. We also propose to expand our scope to include sour taste-related genes. This positional cloning approach will be complemented with behavioral analyses of physiological mechanisms underlying effects of individual genes. These studies, when completed, may provide important new avenues for interventions designed to modify excess food consumption. PUBLIC HEALTH RELEVANCE The sense of taste is the primary sensory system that determines whether a food or beverage will be ingested or rejected. Consequently, understanding the mechanisms underlying this sense is central to our ability to control intake of nutrients and to modulate the excesses of consumption that may underlie diseases such as obesity, hypertension and the metabolic syndrome. We study the taste mechanisms using mouse as a model organism. Our approach, sometimes called positional cloning, is based on chromosomal mapping of genes responsible for variation in taste responsiveness. Previously, we used this approach to identify a locus that codes for a sweet taste receptor. In the current comprehensive proposal, we describe studies designed to continue to identify genes involved in sweet taste. We also propose to expand our scope to include sour taste- related genes. These studies, when completed, may provide important new avenues for interventions designed to modify excess food consumption.