EFFECTS OF MITOGENS ON MUSCLE GROWTH & GENE EXPRESSION

有丝分裂原对肌肉生长的影响

• 批准号: 3456868
• 负责人: NEVIS L FREGIEN
• 金额: $ 8.79万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-07-01 至 1992-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3456868
• 关键词: cell cell interaction; cell differentiation; cell growth regulation; complementary DNA; endonuclease; epidermal growth factor; fibroblast growth factor; gene expression; genetic library; genetic manipulation; genetic regulation; histogenesis; laboratory mouse; mitogens; myoepithelial cell; myogenesis; nucleic acid hybridization; radiotracer; regeneration; tissue /cell culture

The principal objective of this project is to understand, at the molecular level, two main aspects of muscle growth and development. The first set of experiments will use gene transfer technology to study the control of myoblast growth and differentiation by growth factors. The genes encoding the epidermal growth factor receptor and the basic fibroblast growth factor will be inserted and expressed in myogenic cell lines. These cells will then be tested to see if these genetic alterations cause the expected or unexpected changes in the normal program of myoblast proliferation and differentiation. Further experiments, including a molecular genetic approach to the isolation of the fibroblast growth factor receptor, will be done to elucidate the mechanism of growth factor activity in a differentiation cell system. A second set of experiments will be done using, subtraction cDNA cloning technology, to identify and isolate myoblast genes which are regulated during the determination and proliferation stages of muscle development. Genes which are expressed in response to fibroblast growth factor stimulated proliferation will be cloned. These genes will be characterized to identify proteins which are required during the proliferative stage of myogenesis and to further understand the mechanism of growth factor response. The genes which are activated during the commitment of embryonic cells to the myoblast lineage will also be isolated. These genes will provide the initial characterization of the changes in genetic activity during the period of cell fate determination and the factors controlling this poorly understood stage of development.

本项目的主要目标是了解 分子水平，肌肉生长的两个主要方面和 发展。第一组实验将使用基因转移 研究成肌细胞生长和调控的技术 按生长因子进行分化。编码该基因的 表皮生长因子受体与碱性成纤维细胞生长 因子将被插入并在肌源性细胞系中表达。 然后将对这些细胞进行测试，看看这些基因变化是否 在正常程序中引起预期或意外的更改 成肌细胞的增殖和分化。进一步 实验，包括分子遗传学方法 分离成纤维细胞生长因子受体，将进行 阐明肿瘤细胞生长因子活性的机制 分化细胞系统。第二组实验将是 使用减去cDNA克隆技术进行鉴定和 分离成肌细胞基因，这些基因在 肌肉发育的决定和增殖阶段。 与成纤维细胞生长因子相关的基因表达 被刺激的增殖将被克隆。这些基因将是 其特征是识别在生物合成过程中 肌发生的增殖期，并进一步了解 生长因子反应的机制。这些基因是 在胚胎细胞致力于 成肌细胞的谱系也将被分离。这些基因将提供 遗传活性变化的初步表征 细胞命运决定过程中的影响因素 控制着这一鲜为人知的发展阶段。