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.