Development and Use of Genetic Mouse Models to Study Skeletal Muscle Growth

Growth and maintenance of skeletal muscle mass is critical for long-term health and quality of life because of its contribution to mobility, glucose uptake and fat metabolism. The aims of our research projects are to develop and use genetically modified mice to identify key genes necessary for skeletal muscle growth. My project (P.W.) is to create a double transgenic mouse via cross breeding of individual transgenic mice. First, I will take a mouse that produces the DNA recombination enzyme, Cre, under the control of the Tetracycline Operon promoter (TetO) and breed it against a transgenic mouse carrying the Muscle Creatine Kinase promoter driving the reverse tetracycline-controlled transactivator (rtTA). Once obtained, I will create a triple transgenic to test whether the double transgenic mouse actually maintains proper skeletal muscle specific expression in response to tetracycline. My study (CH) will be to test the hypothesis that a gene that is critical for muscle development, MyoD, is necessary for skeletal muscle growth. We have a mouse in which the MyoD gene has been knocked-out from its genome. I will use a surgical model of skeletal muscle growth (mechanical overload) to test the muscle of these mice. Surgery will be performed on normal and MyoD knockout mice and muscle will be collected from 5-21 days after the surgery. Muscle growth will be evaluated by measuring mass, total protein and total DNA. The results of this study will determine whether MyoD is necessary for skeletal muscle hypertrophy in response to overload