Physiology of Calcium Appetite

钙食欲的生理学

• 批准号: 8015407
• 负责人: MICHAEL G TORDOFF
• 金额: $ 9.97万
• 依托单位: MONELL CHEMICAL SENSES CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-22 至 2011-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8015407
• 关键词: Address; Agonist; Behavioral; Brain; Breeding; Calcium; Calcium-Sensing Receptors; Candidate Disease Gene; Code; Computer Simulation; Congenic Strain; Consumption; Desire for food; Development; Dimerization; Disease; Electrophysiology (science); Embryo; Gene Expression; Gene Expression Profiling; Genes; Genetic; Genetic Polymorphism; Genome; Homeostasis; Human; Human Genome; Hypertension; Immunochemistry; Immunohistochemistry; In Situ Hybridization; Incidence; Ingestion; Lead; Link; Location; Magnesium; Methods; Minerals; Molecular Conformation; Mouse Strains; Mus; Obesity; Osteoporosis; Perception; Physiological; Physiology; Population; Premenstrual syndrome; Production; Proteins; Quantitative Trait Loci; Receptor Gene; Recommendation; Research; Saccharin; Signal Transduction; Site; Solutions; System; Taste Perception; Testing; Time; Tissues; Work; calcium intake; calcium metabolism; congenic; consomic; drinking; gene discovery; kidney cell; novel; preference; public health relevance; receptor; response; sweet receptor; sweet taste perception; treatment strategy

DESCRIPTION (provided by applicant): Low voluntary calcium intakes have been implicated in several diseases that afflict the U.S. population including osteoporosis, hypertension, obesity, and premenstrual syndrome. But despite many recommendations to increase calcium intake there has been almost no research to understand why calcium intakes are so low. This project will address this question by identifying and characterizing some of the physiological and genetic controls that underlie calcium consumption. Two aims are proposed in this renewal application. The first is to identify genes responsible for the consumption of calcium. In Aim 1.1, congenic and consomic mice will be bred in order to isolate small chromosomal fragments containing consumption-related genes. In Aim 1.2, candidate genes in each fragment will be assessed using a combination of in silico methods and gene expression studies. The second aim is to characterize the modes and sites of action of two genes that this project has already implicated in the control of calcium consumption; the calcium-sensing receptor, Casr, and the sweet taste receptor, Tas1r3. This will be done by comparing the receptor activity of a mouse strain that avoids calcium (the C57BL/6J or B6 strain) with a strain that drinks calcium avidly (the PWK/PhJ or PWK strain). The plan is to use an HEK cell expression system to compare the physiological responses of B6 and PWK forms of CaSR and T1R3 (Aim 2.1), in situ hybridization, real-time PCR, and immunochemistry to characterize the expression of the B6 and PWK forms of CaSR and T1R3 in taste tissue (Aim 2.2), and gustatory electrophysiology to determine the functional significance of any differences between the two strains in physiological response or location of CaSR and T1R3 (Aim 2.3). Aim 1 will lead to the discovery of genes involved in regulating the ingestion and metabolism of calcium. Aim 2 will test the possibility that a specific receptor or pair of receptors transduce calcium taste. Understanding the mechanisms underlying calcium perception is an important step toward answering the question of why calcium intakes are so low. Given the many similarities between the mouse and human genome, such studies in mice will have direct relevance for the control of calcium consumption by humans, and thus the many diseases associated with excess or insufficient calcium intake. PUBLIC HEALTH RELEVANCE: This project investigates the physiological and genetic controls of calcium intake and preference. Low calcium intakes are associated with several diseases including osteoporosis, hypertension and premenstrual syndrome. An understanding of how calcium consumption is controlled will lead to the development of effective strategies and treatments to increase calcium intake and thus reduce the incidence of these calcium- related diseases.

描述（由申请人提供）：低自愿钙摄入量与困扰美国人群的几种疾病有关，包括骨质疏松症、高血压、肥胖和经前综合征。但是，尽管有很多增加钙摄入量的建议，但几乎没有研究来理解为什么钙摄入量如此之低。这个项目将通过确定和描述钙摄入背后的一些生理和遗传控制来解决这个问题。在这个更新申请中提出了两个目标。首先是确定与钙消耗有关的基因。在Aim 1.1中，为了分离出含有消费相关基因的小染色体片段，将培育基因型和经济型小鼠。在Aim 1.2中，将使用计算机方法和基因表达研究相结合的方法评估每个片段中的候选基因。第二个目的是描述两个基因的作用模式和位点，这个项目已经涉及到钙消耗的控制；钙感应受体Casr和甜味受体Tas1r3。这将通过比较不摄入钙的小鼠品系（C57BL/6J或B6品系）和大量摄入钙的小鼠品系（PWK/PhJ或PWK品系）的受体活性来完成。计划是使用HEK细胞表达系统比较B6的生理反应和PWK CaSR形式和T1R3 2.1 (Aim),原位杂交,实时PCR和免疫化学特征的表达的B6和PWK形式CaSR和味觉T1R3组织2.2 (Aim),和味觉电生理决定的功能意义两个菌株的生理反应之间的任何差异或位置CaSR和T1R3 2.3 (Aim)。目的1将导致发现参与调节钙的摄入和代谢的基因。目的2将测试一个特定受体或一对受体转导钙味道的可能性。了解钙感知机制是回答钙摄入量如此之低的重要一步。鉴于小鼠和人类基因组之间的许多相似之处，此类小鼠研究将与人类钙消耗的控制直接相关，因此与钙摄入过量或不足相关的许多疾病。公共卫生相关性：本项目调查钙摄入和偏好的生理和遗传控制。低钙摄入与多种疾病有关，包括骨质疏松症、高血压和经前综合症。了解钙的摄入是如何控制的，将有助于制定有效的策略和治疗方法来增加钙的摄入，从而减少这些钙相关疾病的发病率。