Production of Animal Models for Marbling by Introducing The Bovine ADAM12 Gene

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ADAM12 is a member of the ADAM (a disintegrin and metalloprotease) family, and recently has been suggested to function in regulation of myogenesis and adipogenesis. It is also reported that the transgenic mice expressing human ADAM12 specifically in muscle tissue exhibit the intramuscular fat deposition. As these phenotypes are similar to the beef marbling, we produced the transgenic mice expressing the bovine ADAM12 gene specifically in muscle tissue to establish the animal models for marbling.Three transgenes (MCK-bADAM12 C3, TRC and MP) were prepared from the bovine ADAM12 cDNA. MCK-bADAM12 C3 encodes a membrane-anchored ADAM12 protein consisting of the prodomain, the metalloprotasase, disintegrin, cystein-rich, and transmenbrane domains and cytoplasmic-tail. MCK-bADAM12 TRC encodes a secreted-form protein consisting of the whole extracellular domain. MCK-bADAM12 MP encodes the prodomain and the metalloprotease domain.These transgenes are driven by the mouse muscle creatine kinase (MCK) promoter for the muscle-specific expression.One, two and three transgenic founders were obtained for each of transgenes C3, TRC and MP, respectively. Transgenic individuals were fertile and transmitted the bovine ADAM12 genes to the offsprings.All transgenic lines did not differ from littermate controls in body weight and fat content. However, TRC and MP transgenic mice developed the increased intramuscular fat deposition more than littermate controls, but C3 transgenic mice did not.The observation of similar phenotypes between TRC and MP transgenic mice muscle tissues suggested that ADAM12 metalloprotease domain was sufficient to induce the intramuscular fat deposition.