TASTE AND GENETIC MECHANISMS OF MACRONUTRIENT SELECTION

该项目的长期目标是为味觉和影响常量营养素选择的遗传因素之间的联系提供新的证据。这一建议的总体假设是，不同品系的小鼠对脂肪或碳水化合物来源的不同和不同的偏好是由基因决定的，品系口味偏好的差异(S)促成了这种常量营养素的选择行为。检验这一假设的主要策略将是对行为品味偏好和常量营养素自我选择的研究，共分离分析，以及遗传连锁分析。最近，我们确定了一个有价值的模型来研究味道和饮食选择之间的关系：两个新的小鼠品系对，它们展示了大量营养素选择的对比模式。AKR/J和C57BL/6J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与SWR/J的差异常量营养素选择模型推广到许多其他饮食模式，然而，3选择常量营养素选择模式已被确定为本研究计划中所描述的遗传分析中使用的最准确和最可靠的行为表型。此外，初步数据表明，AKR/J和SWR/J小鼠对玉米油乳剂和苦味蔗糖八醋酸酯(SOA)的偏好也不同。对品尝反应的品系差异的鉴定与常量营养素的选择有关，即有证据表明苦味敏感性是由基因控制的，最近的研究表明苦味敏锐度与对脂肪的偏好有关。因此，特定目标1将使用两瓶偏好测试来研究第二个新菌株对玉米油和SOA的偏好反应。在具体目标2中，将采用F2杂交策略(AKR/J×SWR/J和C57BL/6J×CAST/EI)对行为表型的遗传模式进行遗传分析。大量营养素选择和口味偏好模式不同的两个菌株对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背后存在共同的遗传机制。然而，这项研究计划最重要的潜在结果是能够定位导致常量营养素选择行为的基因的染色体位置。因此，在具体目标3中，将使用数量性状座位(QTL)策略在两个F2群体中进行全基因组筛选的遗传作图研究。这些研究的结果将提供一个新的理解的味道和遗传机制背后的常量营养素选择。

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.