FGF SIGNALING IN BONE GROWTH AND DEVELOPMENT

FGF 信号在骨骼生长和发育中的作用

• 批准号: 2389005
• 负责人: David M Ornitz
• 金额: $ 21.79万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-07-01 至 2001-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2389005
• 关键词: RNase protection assay; acetylcholine; biological signal transduction; bone development; cartilage development; chondrocytes; epiphysis; fibroblast growth factor; gene expression; genetic promoter element; genetically modified animals; growth factor receptors; immunocytochemistry; laboratory mouse; normal ossification; polymerase chain reaction; protein structure; tissue /cell culture

DESCRIPTION (adapted from investigator's abstract): This is a five year RO1 proposal to study the role of FGFR3 and FGF9 in bone development. The objectives of this proposal are to determine how FGFR3 regulates chondrogenesis and how it interacts with other signalling molecules thought to be important for endochondral ossification and to identify the physiological ligands that activate FGFR3 in vivo during endochondral ossification. The first aim will explore the expression of FGFR3 in the growth plates of normal mice using a transgenic mouse in which the LacZ gene is under control of the FGFR3 promoter and by immunohistochemistry. The second aim explores whether ligand affinity is altered by the Ach and TD mutation and whether chondrocyte gene activity is altered in culture. The third aim will ascertain by RT-PCR which FGFs are present in the adult growth plate. In the fourth aim it is proposed to complete a catalog of the expression of FGF9 by organ system ISH, RNAse protection assay, immunolocalization, FGF9-LacZ transgenic and the FGF9 gene structure will be completed.

描述(改编自调查人员摘要)：这是一个五年的RO1 建议研究FGFR3和FGF9在骨发育中的作用。这个 这项提案的目标是确定FGFR3如何监管 软骨形成及其与其他信号分子的相互作用 对软骨内骨化很重要，并确定 软骨内激活体内FGFR3的生理配体 骨化。第一个目的是探讨FGFR3在大鼠脑内的表达。 利用LacZ基因转基因小鼠建立正常小鼠生长板 是由FGFR3启动子和免疫组织化学控制的。这个 第二个目的是探讨Ach和TD是否改变了配体的亲和力 突变和软骨细胞基因活性在培养过程中是否发生改变。这个 第三个目的是通过RT-PCR法确定成人体内存在哪些FGFs 生长板。在第四个目标中，建议完成一份 脏器系统原位杂交、核糖核酸酶保护法检测FGF9的表达 免疫定位、FGF9-LacZ转基因和FGF9基因结构 完成。