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NOVEL GENE DISCOVERED IN THE HEART

在心脏中发现的新基因

基本信息

批准号：
6389849
负责人：
WILLIAM C CLAYCOMB
金额：
$ 21.32万
依托单位：
LSU HEALTH SCIENCES CENTER
依托单位国家：
美国
项目类别：
财政年份：
1999
资助国家：
美国
起止时间：
1999-07-05 至 2003-07-04
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6389849
关键词：
cardiac myocytes cell line cell proliferation developmental genetics gene expression genetic mapping immunoprecipitation laboratory rat muscle proteins nucleic acid sequence tissue /cell culture yeast two hybrid system

项目摘要

Development of the heart requires the precise spatial and temporal control of gene expression for proliferation and differentiation. During embryonic and early neonatal development, the heart grows by cell proliferation. Further growth is later established through cell enlargement, or cardiac hypertrophy. Cardiac muscle cell proliferation appears to be regulated by a separate program, distinct from the program which controls differentiation of the myocyte, unlike most other cell types. The mechanisms governing the control of cardiomyocyte proliferation are yet to be established. An understanding of these mechanisms will provide an avenue of opportunity to manipulate cellular proliferation to replace and/or repair damaged tissue sustained from cardiovascular disease. We have identified, cloned and sequenced a novel gene (TAP) in the heart which is expressed in association with myocyte proliferation. Preliminary western analysis show that the Tap protein is expressed only in the dividing cardiomyocyte and is virtually absent from the non dividing myocyte. Our hypothesis predicts that TAP is a necessary component of a signal transduction pathway required for cardiomyocyte proliferation. Our long term goal is to determine the function of Tap in the dividing myocyte. Our specific aims are to: (1) Identify cellular proteins which associated with Tap in the cardiomyocyte using the yeast two-hybrid screen and co-immunoprecipitation in order to determine how Tap may function in the cell. (2) To begin to functionally characterize Tap by over expressing and blocking its expression in cultured adult, 21-day postnatal and embryonic rat ventricular cardiomyocytes and in the HL-1 cardiac muscle cell line. Since this gene is entirely novel these studies will provide the first indication of the functional role of TAP in the myocyte, and provide a foundation for the design of rational, future in depth studies.

心脏的发育需要对增殖和分化的基因表达进行精确的空间和时间控制。在胚胎和新生儿早期发育期间，心脏通过细胞增殖生长。随后通过细胞增大或心脏肥大建立进一步生长。心肌细胞增殖似乎是由一个单独的程序，不同于程序控制分化的肌细胞，不像大多数其他类型的细胞。控制心肌细胞增殖的机制尚未建立。对这些机制的理解将提供一个机会，操纵细胞增殖，以取代和/或修复受损组织持续心血管疾病。我们已经确定，克隆和测序一个新的基因（TAP）在心脏中表达与心肌细胞增殖。初步的Western分析显示Tap蛋白仅在分裂的心肌细胞中表达，而在非分裂的心肌细胞中几乎不表达。我们的假设预测，TAP是心肌细胞增殖所需的信号转导途径的必要组成部分。我们的长期目标是确定Tap在分裂的肌细胞中的功能。我们的具体目标是：（1）利用酵母双杂交筛选和免疫共沉淀技术鉴定心肌细胞中与Tap相关的细胞蛋白，以确定Tap在细胞中的功能。 (2)开始通过在培养的成年、出生后21天和胚胎大鼠心室心肌细胞和HL-1心肌细胞系中过表达和阻断其表达来功能性地表征Tap。由于该基因是全新的，这些研究将首次表明TAP在肌细胞中的功能作用，并为设计合理的未来深入研究提供基础。