ADAMS IN MUSCLE DEVELOPMENT

亚当斯在肌肉发育中的作用

• 批准号: 6375142
• 负责人: EVA S ENGVALL
• 金额: $ 35.2万
• 依托单位: SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-10 至 2002-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6375142
• 关键词: cell differentiation; embryonic stem cell; gene targeting; genetically modified animals; immunofluorescence technique; laboratory mouse; ligands; membrane proteins; metalloendopeptidases; muscle cells; muscle proteins; myogenesis; northern blottings; polymerase chain reaction

DESCRIPTION: ADAMs/MDCs belong to a novel family of transmembrane proteins related to snake venom and metalloproteases. Members of the ADAM family are composed of a prodomain, metalloprotease, disintegrin, cysteine-rich, EGF-like transmembrane domains, and a cytoplasmic domain of variable length. ADAM 12 an 13 are closely related and are both expressed in muscle. ADAM 12 was previousl described in the mouse and is active in homotypic cell differentiation. ADAM 1 been described only in Xenopus. The role of ADAMs 12 and 13 in the mouse muscl development and disease will be studied. The interactions of ADAM 12 with cell surface ligands will be characterized by using cell adhesion assays. Intracellular proteins interacting with the cytoplasmic domain of ADAM 12 will be identified and characterized by using the yeast two hybrid system. The role of ADAM 12 in development and differentiation will be studied by determining the effects of overexpression of ADAM12 domains in vivo and in vitro. The importance of ADAM 12 and ADAM 13 in development of the mouse will be determined by inactivation of the genes by homologous recombination in embryonic stem cells. The expression and localization of ADAM12 and 13 and other ADAMs in normal and diseased muscle will be determined by PCR, northern blotting, and indirect immunofluorescence. This research will generate basic information on the ADAM family of protein, generate new model systems for research, and contribute new insights in the biology of muscle.

描述：ADAMS/MDCs属于一个新的跨膜蛋白家族 与蛇毒和金属蛋白酶有关。亚当家族的成员是 由原结构域、金属蛋白酶、去整合素、富含半胱氨酸、 EGF样跨膜结构域，以及长度可变的细胞质结构域。 亚当12和13是密切相关的，都在肌肉中表达。亚当12 以前在小鼠中描述过，在同型细胞中是活跃的 差异化。亚当1号只在非洲爪哇被描述过。亚当斯的角色 12和13在小鼠肌肉中的发育和疾病将被研究。这个 ADAM 12与细胞表面配体的相互作用将通过 使用细胞黏附试验。与细胞内蛋白相互作用的蛋白质 ADAM 12的细胞质结构域将通过使用 酵母双杂交系统。ADAM 12在发育和发育中的作用 将通过确定过度表达的影响来研究分化 ADAM12结构域在体内和体外的表达。亚当十二世和亚当的重要性 13在鼠标的发育过程中将由失活的 胚胎干细胞中同源重组的基因。表达方式 ADAM12和13及其他ADAMS在正常和疾病中的定位 肌肉将通过聚合酶链式反应、Northern印迹和间接检测来确定 免疫荧光。这项研究将产生关于 亚当蛋白质家族，为研究产生新的模型系统，以及 在肌肉生物学方面贡献新的见解。