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CELLULAR RETINOIC ACID-BINDING PROTEIN-1

细胞视黄酸结合蛋白-1

基本信息

批准号：
2458799
负责人：
Li-Na Wei
金额：
$ 10.55万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
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/2458799
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

项目摘要

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是一组相关类维生素A的统称，对动物的正常发育和生长至关重要。太少过多会导致各种各样的生物缺陷，并此外，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。先前的研究表明细胞视黄酸结合蛋白（CRABP）起着重要作用。在维持细胞内RA浓度恒定方面起主要作用。然而，由于CRABP在这方面是如此重要，突变和其他大大减少或消除这种蛋白质操作通常对生物体是致命的，因此不能用于研究CRABP功能。这项建议的主要目标是了解积极和 CRABP基因的负调控元件，并产生特定的变化所以它的表达在动物中会改变但不会消失。具体来说，我们将1。确定基因的区域，它的调节，通过系统地删除5'区域的部分，与LacZ报告基因融合的基因，和2.制造转基因小鼠， CRABP在正常情况下不表达该蛋白的组织中表达，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，以及最终导致更好地预防/治疗应用维生素 A在人类