The Transgenic Animal Core will provide investigators in the four Projects with uniformly maintained, specific-pathogen-free colonies of aging knockout/transgenic mice with alterations in the gene coding for Cu/Zn-superoxide dismutase (Sod1). In addition, the Transgenic Animal Core will generate conditional knockout mice for Sod1, which will be available for future studies. An aging colony of the following knockout/transgenic mouse models and their wild type littermates will be maintained in the Transgenic Animal Core: 1) mice null for Sod1 in all tissues 2) Sodf^mice that express Sod1 in skeletal muscle (SodT'~ (M+) mice), and 3) Socf-/""""""""Amice that express Sod1 in neurons (Socff'~(N+) mice).
The specific aims of the Transgenic Animal Core are as follows: 1. To maintain breeding colonies of the knockout/transgenic mice for the production of male knockout/transgenic mice that will be used in the Program Project. 2. To maintain aging colonies of male Socff'"""""""", SodT'~(M+), SodT/~(N+), and Socf7*/+ mice. Animals from these colonies will be used in the four Projects for the experiments described in this proposal at the following age. 3. To provide specific projects with special mutant mouse models crossed to the SodT''mice, e.g., the NFicB reporter mice, NFxB knockout mice (p50""""""""A), and nNOS transgenic mice. 4. To produce conditional knockout mice (Sod 1 A3,4^) that do not express Cu/ZnSOD in skeletal muscle or neurons. The Transgenic Animal Core will generate several lines of novel transgenic/knockout mice deficient in Cu/Zn-superoxide dismutase in neuronal and muscle tissue. These mice will allow investigators in this program project to define the tissue(s) responsible for the age-related loss of muscle arising from oxidative stress.
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