TASTE AND GENETIC MECHANISMS OF MACRONUTRIENT SELECTION

大量营养素选择的口味和遗传机制

• 批准号: 6381500
• 负责人: BRENDA K SMITH RICHARDS
• 金额: $ 21.64万
• 依托单位: LSU PENNINGTON BIOMEDICAL RESEARCH CTR
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-01 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6381500
• 关键词: animal breeding; behavioral /social science research tag; behavioral genetics; dietary carbohydrates; dietary lipid; genetic models; genetic strain; laboratory mouse; linkage mapping; nutrient intake activity; nutrition related tag; phenotype; preference; quantitative trait loci; taste

The long-term goal of this project is to provide new evidence for a link between taste and genetic factors that influence macronutrient selection. The overall hypothesis of this proposal is that distinct and contrasting preferences for fat or carbohydrate sources across mouse strains are genetically determined and that strain differences in taste preference(s) contribute to this macronutrient selection behavior. The primary strategies used to test this hypothesis will be studies of behavioral taste preference and macronutrient self-selection, cosegregation analysis, and genetic linkage analysis. Recently we identified a valuable model for investigating the relationship between taste and dietary selection: two novel mouse strain pairs that exhibit contrasting patterns of macronutrient selection. AKR/J and C57BL/6J mice select/consume a higher proportion of fat while the SWR/J and CAST/Ei mice select/consume a higher proportion of carbohydrate. The AKR/J vs. SWR/J model of differential macronutrient selection generalizes to many other diet paradigms however the 3-choice macronutrient selection paradigm has been identified as the most accurate and reliable behavioral phenotype to be used in the genetic analyses described in this research plan. Moreover preliminary data indicate that AKR/J and SWR/J mice also differ in their taste preferences for corn oil emulsions and for the bitter tastant sucrose octaacetate (SOA). The identification of strain differences in taste responsiveness is relevant to macronutrient selection, i.e., there is evidence for genetic control of bitter taste sensitivity, and recent studies suggest an association between bitter taste acuity and the preference for fat. Thus Specific Aim 1 will examine the taste preference responses to corn oil and SOA in the second novel strain pair (C57BL/6J and CAST/Ei), using two-bottle preference tests. In Specific Aim 2, a genetic analysis of the mode of inheritance of the behavioral phenotypes will be performed using an F2 intercross breeding strategy (AKR/J x SWR/J and C57BL/6J x CAST/Ei). The availability of two strain pairs with contrasting patterns of macronutrient selection and taste preferences will also permit a cosegregation analysis in the F2 progeny to determine whether there is evidence for a common genetic mechanism underlying differences in fat or carbohydrate preference and bitter taste sensitivity. However the most important potential result of this research plan is the ability to locate the chromosomal positions of genes underlying the macronutrient selection behavior. Thus in Specific Aim 3, a genetic mapping study will be carried out using the quantitative trait loci (QTL) strategy of performing a whole genome screen in two F2 populations. The results of these studies will provide a new understanding of the taste and genetic mechanisms underlying macronutrient selection.

该项目的长期目标是为味觉与影响大量营养素选择的遗传因素之间的联系提供新的证据。 该提议的总体假设是，不同小鼠品系对脂肪或碳水化合物来源的不同和对比偏好是由遗传决定的，并且味觉偏好的品系差异有助于这种大量营养素选择行为。 检验这一假设的主要策略是行为味觉偏好和大量营养素自我选择的研究、共分离分析和遗传连锁分析。 最近，我们确定了一个有价值的模型，研究口味和饮食选择之间的关系：两个新的小鼠品系对，表现出对比模式的宏量营养素选择。AKR/J和C57 BL/6 J小鼠选择/消耗较高比例的脂肪，而SWR/J和CAST/Ei小鼠选择/消耗较高比例的碳水化合物。 AKR/J vs. SWR/J差异大量营养素选择模型可推广到许多其他饮食模式，但3种选择大量营养素选择模式已被确定为用于本研究计划中描述的遗传分析的最准确和可靠的行为表型。 此外，初步数据表明，AKR/J和SWR/J小鼠在对玉米油乳剂和苦味促味剂蔗糖八乙酸酯（SOA）的味觉偏好方面也存在差异。 味觉反应性的菌株差异的鉴定与大量营养素选择有关，即，有证据表明苦味敏感性受遗传控制，最近的研究表明苦味敏锐度与对脂肪的偏好之间存在关联。 因此，具体目标1将使用两瓶偏好测试来检查第二新菌株对（C57 BL/6 J和CAST/Ei）中对玉米油和SOA的味觉偏好响应。 在特定目标2中，将使用F2杂交育种策略（AKR/J x SWR/J和C57 BL/6 J x CAST/Ei）对行为表型的遗传模式进行遗传分析。 两个菌株对的大量营养素选择和口味偏好的对比模式的可用性也将允许在F2后代中进行共分离分析，以确定是否有证据表明脂肪或碳水化合物偏好和苦味敏感性差异的共同遗传机制。 然而，这项研究计划最重要的潜在成果是能够定位大量营养素选择行为背后的基因的染色体位置。 因此，在具体目标3中，将使用在两个F2群体中进行全基因组筛选的数量性状基因座（QTL）策略进行遗传作图研究。 这些研究的结果将提供一个新的理解的味道和遗传机制的基础宏量营养素的选择。