Genetic controls of mineral consumption

矿物质消耗的基因控制

• 批准号: 8672784
• 负责人: MICHAEL G TORDOFF
• 金额: $ 0.64万
• 依托单位: MONELL CHEMICAL SENSES CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8672784
• 关键词: Affect; Bioinformatics; Calcium; Candidate Disease Gene; Computer Simulation; Congenic Mice; Congenic Strain; Consomic Strain; Consumption; Dietary Intervention; Disease; Electrophysiology (science); Etiology; Food; Gene Expression Profiling; Genes; Genetic; Genetically Engineered Mouse; Genome; Genotype; Goals; Homeostasis; Hypertension; Intake; Knowledge; Link; Magnesium; Malignant Neoplasms; Measures; Methods; Minerals; Mus; Nerve; Obesity; Oral; Osteoporosis; Physiological; Policies; Population; Potassium; Production; Quantitative Trait Loci; Saccharin; Site; Sodium; Solutions; Taste Perception; Testing; Work; base; calcium intake; chorda tympani; congenic; consomic; drinking; gene discovery; preference; public health relevance; response; treatment strategy

DESCRIPTION (provided by applicant): This is a project to discover the genetic controls that are responsible for the consumption of calcium, magnesium, potassium and sodium. We have already identified several quantitative trait loci (QTLs) related to consumption of these minerals. We propose here to identify the genes underlying some of these QTLs. To do this, we will first produce congenic strains of mice with introgressed QTL- containing chromosomal fragments. This will be done using either a classic selection-by-genotype approach or by taking advantage of recently developed consomic strains. As an example of the classic approach, we propose to complete production of congenic mouse lines that isolate a QTL on Chr 17 that has impressively high LOD scores for CaCl2 preference (LOD = 45) and saccharin preference (LOD = 100). As an example of the consomic-origin approach, we propose to produce congenic lines to isolate a QTL on Chr 5, with a LOD score for NaCl preference of 8.5. To our knowledge, this will be the first QTL for sodium consumption to be characterized. Once congenic strains are established, we will evaluate candidate genes residing in the congenic interval. This will be done using a combination of in silico analyses, gene expression profiling, and related methods. If necessary, licking responses and gustatory electrophysiology will be recorded to determine the site of gene action. The goal will be to reduce the list of candidate genes to a number that can be assessed using genetically engineered mice. Finding genes responsible for the consumption of minerals will help us understand why people do not consume satisfactory amounts of them. Low intakes of calcium, magnesium and potassium, and high intakes of sodium, have been linked to the etiology of many diseases affecting the U.S. population, including hypertension, obesity, osteoporosis, and some forms of cancer. The results of the studies proposed here will expose the mechanisms underlying mineral consumption. With this knowledge, it will be possible to target new treatments and strategies that rectify the inadequate intakes and thus ameliorate or eliminate the diseases.

描述（由申请人提供）：这是一个发现负责消耗钙，镁，钾和钠的遗传控制的项目。我们已经确定了与这些矿物质消耗有关的几个定量性状基因座（QTL）。我们在这里建议确定其中一些QTL的基因。为此，我们将首先用含有染色体碎片的QTL-旋转QTL的小鼠产生先天性菌株。这将使用经典的逐型方法或利用最近开发的综合菌株来完成。作为经典方法的一个例子，我们建议完成隔离ChR 17上QTL的先天小鼠系的生产，该QTL具有CACL2偏好（LOD = 45）和糖精蛋白偏好（LOD = 100）的高度高LOD评分（LOD = 45）。作为综合蛋白方法方法的一个例子，我们提议生产先行线以隔离ChR 5上的QTL，而NaCl偏好为8.5的LOD评分。据我们所知，这将是要表征钠消耗的第一个QTL。一旦建立了先天性菌株，我们将评估居住在股间隔的候选基因。这将使用硅分析，基因表达分析和相关方法的组合来完成。如有必要，将记录舔反应和味觉电生理学，以确定基因作用部位。目的是将候选基因列表减少到可以使用基因工程小鼠进行评估的数字。寻找负责矿物质消耗的基因将有助于我们了解为什么人们不会消耗令人满意的含量。钙，镁和钾的摄入量低，以及钠的高摄入量与许多影响美国人群的疾病的病因有关，包括高血压，肥胖，骨质疏松症和某些形式的癌症。此处提出的研究结果将暴露矿物消耗的基础机制。有了这些知识，将有可能针对新的治疗方法和策略，以纠正摄入量不足，从而改善或消除疾病。