MEMBRANE CHANGES IN NEUROLOGIC AND AGING DISEASES

神经系统和衰老疾病中的膜变化

• 批准号: 3120061
• 负责人: MARGUERITE M KAY
• 金额: $ 11.38万
• 依托单位: TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-07-12 至 1992-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3120061
• 关键词: DNA; band 3 protein; erythrocytes; gene expression; genetics; human subject; human tissue; nucleic acid sequence; nucleic acid structure; reticulocytes; DNA; band 3 protein; erythrocytes; gene expression; genetics; human subject; human tissue; nucleic acid sequence; nucleic acid structure; reticulocytes

The purpose of the proposed study is to investigate 3 newly discovered, unique defects in band 3, the major anion transport and acid-base balance protein. One of the defects represents a recognized autosomal recessive disease and is associated with ion and glucose transport abnormalities and a serious progressive neuropsychiatric disorder (familial amyotrophic chorea with acanthocytosis). Another disease presents biochemically and immunologically as accelerated aging of young and middle aged red blood cells. The reticulocyte count is -20%. The third disease is characterized by acanthocytosis and increase anion transport. It is called "high- molecular weight band 3" because there is an addition of several peptides in the anion transport region. Band 3 is a ubiquitous protein. Like the RBC proteins spectrin, ankyrin, 4.1, and actin, it is present in brain and all other cells examined. The specific aims of this project are to (1) determine what functional defects are associated with band 3 structural defects; (2) define the structural defects in terms of band 3 domains and amino acid sequence; (3) determine alterations in DNA sequence of the band 3 gene of affected individuals by sequencing regions of the gene which correspond to regions of the protein which appear altered in the peptide maps of the patient's band 3 proteins; (4) determine the mode of inheritance of band 3 defects in kindreds; (5) identify other defects in band 3 in the population.

拟议的研究的目的是研究3个新发现的， 带3的独特缺陷，主要阴离子传输和酸碱平衡 蛋白质。其中一个缺陷代表公认的常染色体隐性 疾病，与离子和葡萄糖转运异常有关 以及严重的进行性神经精神疾病（家族性肌萎缩症 与刺刺细胞增多症的唱片）。另一种疾病在生化和 在免疫学上，年轻和中年红血的衰老加速 细胞。网状细胞计数为-20％。第三种疾病的特征是 通过棘细胞增多症并增加阴离子的转运。它称为“高 - 分子量带3“，因为有几种肽的添加 在阴离子运输区域。带3是一种无处不在的蛋白质。喜欢 RBC蛋白质谱，Ankyrin，4.1和肌动蛋白，它存在于大脑中 以及所有其他检查的细胞。 该项目的具体目的是（1）确定什么功能 缺陷与3条结构缺陷有关； （2）定义 结构缺陷在带3个结构域和氨基酸序列方面； （3）确定受影响的频带3基因的DNA序列的改变 通过对应区域的基因的测序区域进行测序区域 在患者的肽图中发生改变的蛋白质 带3蛋白； （4）确定频带3缺陷的继承方式 在Kindreds中； （5）确定人群中频段3中的其他缺陷。