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 forCu/Zn-superoxide dismutase (Sod1). In addition, the Transgenic Animal Core will generate conditionalknockout mice for Sod1, which will be available for future studies. An aging colony of the followingknockout/transgenic mouse models and their wild type littermates will be maintained in the TransgenicAnimal 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 theTransgenic Animal Core are as follows:1. To maintain breeding colonies of the knockout/transgenic mice for the production of maleknockout/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 thesecolonies 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., theNFicB 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 muscleor neurons.The Transgenic Animal Core will generate several lines of novel transgenic/knockout mice deficient inCu/Zn-superoxide dismutase in neuronal and muscle tissue. These mice will allow investigators in thisprogram project to define the tissue(s) responsible for the age-related loss of muscle arising from oxidativestress.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
2P01AG020591-06A1
Application #
7436691
Study Section
Special Emphasis Panel (ZAG1-ZIJ-5 (J4))
Project Start
2008-05-01
Project End
2013-04-30
Budget Start
2008-05-01
Budget End
2009-04-30
Support Year
6
Fiscal Year
2008
Total Cost
$192,580
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
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Zhang, Yiqiang; Unnikrishnan, Archana; Deepa, Sathyaseelan S et al. (2017) A new role for oxidative stress in aging: The accelerated aging phenotype in Sod1-/- mice is correlated to increased cellular senescence. Redox Biol 11:30-37
Deepa, Sathyaseelan S; Bhaskaran, Shylesh; Espinoza, Sara et al. (2017) A new mouse model of frailty: the Cu/Zn superoxide dismutase knockout mouse. Geroscience 39:187-198
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Sakellariou, Giorgos K; Pearson, Timothy; Lightfoot, Adam P et al. (2016) Long-term administration of the mitochondria-targeted antioxidant mitoquinone mesylate fails to attenuate age-related oxidative damage or rescue the loss of muscle mass and function associated with aging of skeletal muscle. FASEB J 30:3771-3785
Jackson, Malcolm J (2016) Reactive oxygen species in sarcopenia: Should we focus on excess oxidative damage or defective redox signalling? Mol Aspects Med 50:33-40

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