ADAMS IN MUSCLE DEVELOPMENT

亚当斯/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 由前结构域、金属蛋白酶、去整合素、富含半胱氨酸 EGF样跨膜结构域和可变长度的胞质结构域。 ADAM 12和13密切相关，都在肌肉中表达。 亚当12 先前在小鼠中描述，并且在同型细胞中具有活性 分化 ADAM 1仅在非洲爪蟾中被描述。 亚当斯的作用 将研究12和13在小鼠肌肉发育和疾病中的作用。 的 ADAM 12与细胞表面配体的相互作用的特征在于： 使用细胞粘附测定。 细胞内蛋白质与 ADAM 12的胞质结构域将通过使用 酵母双杂交系统 自动协调机制第12条在发展和 将通过确定过表达的影响来研究分化 的ADAM 12结构域在体内和体外。 第12章和亚当 13在小鼠发育中的作用将通过灭活 在胚胎干细胞中进行同源重组。 表达 ADAM 12和13以及其他亚当斯在正常和病变组织中的定位 肌肉将通过PCR、北方印迹和间接免疫荧光法测定。 免疫荧光 这项研究将产生关于 ADAM蛋白质家族，产生新的研究模型系统， 为肌肉生物学提供了新的见解。

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.