NUCLEIC ACID STUDIES OF ANTIARSONATE HYBRIDOMAS

抗胂酸杂交瘤的核酸研究

• 批准号: 2060724
• 负责人: HALEY O TUCKER
• 金额: $ 18.1万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-09-30 至 1995-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2060724
• 关键词: B lymphocyte; DNA binding protein; antibody formation; arsenic; fusion gene; genetic promoter element; genetic transcription; hybridomas; immunoglobulin genes; laboratory mouse; laboratory rabbit; molecular cloning; tissue /cell culture; transfection

The original goals of this project concerned the expression of anti-arsonate hybridomas. In particular, we hoped to understand something of the germline contribution to the anti-arsonate immune response. These goals have been largely met. During the past five years, this grant also funded work concerning transcription initiation through the VH-promoter-associated octamer motif. The VH genes of the arsonate system as well as other murine VH and VL genes were used to gain insight into the factors that regulated immunoglobulin gene expression. The present application is wholly directed toward this latter issue and is divided into three aims: First, we seek to continue our studies on the "conventional" ubiquitous octamer binding protein, OTF1, which promotes B-cell stage-specific transcription in lieu of OTF2. Aims 2 and 3 focus on two types of "unconventional" octamer-binding proteins (i.e., lack the prototypic POU domain of OTF1, OTF2 and related factors). One of these, P3, represents a new class of DNA-binding proteins and shares striking homology with a Drosophila protein involved in visual processing. The other is the well-known Ku antigen, a DNA-associated nuclear protein recognized by sera from patients with certain autoimmune diseases. We propose studies of both a molecular biological as well as a biochemical nature that should provide insight into the mechanisms of promoter region function in the murine immune and nervous systems.

该项目的最初目标涉及表达 抗胂酸杂交瘤。 我们特别希望了解 种系对抗胂酸盐免疫的贡献 回复。 这些目标已基本实现。在过去的五年里， 这笔赠款还资助了有关转录启动的工作 VH 启动子相关的八聚体基序。 胂酸盐的VH基因 系统以及其他小鼠 VH 和 VL 基因被用来获得洞察力 调节免疫球蛋白基因表达的因素。 本申请完全针对后一个问题并且 分为三个目标：第一，我们寻求继续研究 “传统”普遍存在的八聚体结合蛋白 OTF1，它促进 B 细胞阶段特异性转录代替 OTF2。 目标 2 和 3 重点 关于两种类型的“非常规”八聚体结合蛋白（即，缺乏 OTF1、OTF2 和相关因子的原型 POU 结构域）。 其中之一， P3，代表一类新的 DNA 结合蛋白，具有惊人的共同点 与参与视觉处理的果蝇蛋白具有同源性。 这 另一个是众所周知的 Ku 抗原，一种 DNA 相关核蛋白 由患有某些自身免疫性疾病的患者的血清识别。 我们建议对分子生物学和 生化性质应该提供对机制的深入了解 启动子区在小鼠免疫和神经系统中发挥作用。