CELLULAR RETINOIC ACID-BINDING PROTEIN-1

细胞视黄酸结合蛋白-1

• 批准号: 3464904
• 负责人: Li-Na Wei
• 金额: $ 9.23万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-08-01 至 1998-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3464904
• 关键词: DNA footprinting; embryo /fetus culture; fusion gene; gene expression; genetic manipulation; genetic regulatory element; genetically modified animals; growth /development; laboratory mouse; nucleic acid sequence; nutrition related tag; reporter genes; retinoid binding proteins

Vitamin A, the collective name for a group of related retinoids, is essential for normal development and growth in animals. Too little of too much results in a wide variety of biological defects, and in addition, increases toxicity caused by alcohol and various environmental toxins. The biologically active retinoid is retinoic acid (RA), and its concentration within cells is critical to health. Previous studies have indicated that a cellular retinoic acid-binding protein (CRABP) plays a major role in maintaining intracellular RA at a constant concentration. However, because CRABP is so vital in this regard, mutation and other manipulation that greatly reduce or eliminate this protein are generally lethal to the organism, and hence cannot be used to study CRABP function. The major goal of this proposal is to understand the positive and negative regulatory elements of CRABP gene and to create specific changes in this gene so its expression is altered but not eliminated in animals. Specifically, we will 1. determine the region of the gene essential for its regulation, by systematically deleting portions of the 5' region of the gene fused to a LacZ reporter, and 2. create transgenic mice in which CRABP is expressed in tissues normally not expressing this protein, as well as animals in which normal CRABP expression is blocked. Taken together, these studies should illustrate the interaction of RA and CRABP and the mechanisms that regulate intracellular RA concentration, and ultimately lead to better preventive/therapeutic application of vitamin A in humans.

维生素 A 是一组相关视黄醇的统称，是 对于动物的正常发育和生长至关重要。 太少了 过多会导致多种生物缺陷，并导致 此外，还会增加酒精和各种环境引起的毒性 毒素。 具有生物活性的类维生素A是视黄酸（RA），其 细胞内的浓度对健康至关重要。 之前的研究有 表明细胞视黄酸结合蛋白（CRABP）发挥着 维持细胞内 RA 浓度恒定的主要作用。 然而，由于 CRABP 在这方面如此重要，突变和其他 大大减少或消除这种蛋白质的操作通常是 对生物体是致命的，因此不能用于研究 CRABP 功能。 该提案的主要目标是了解积极和 CRABP基因的负调控元件并产生特定的变化 因此它的表达在动物中发生改变但并未消除。 具体来说，我们将 1. 确定基因必需的区域 它的调节，通过系统地删除 5' 区域的部分 将该基因与 LacZ 报告基因融合，并且 2. 创建转基因小鼠，其中 CRABP 在通常不表达该蛋白的组织中表达，如 以及正常 CRABP 表达被阻断的动物。 采取 总之，这些研究应该说明 RA 和 CRABP 的相互作用 以及调节细胞内 RA 浓度的机制，以及 最终导致维生素更好的预防/治疗应用 A在人类中。