The overall objective of the Mouse Management and Pathology Core (Core B) is to raise, maintain, and provide cohorts of specific pathogen-free and genetically standardized p66Shc-/- knockout mice for all research projects in this program project. Also, the core will raise and maintain mice on calorie-restricted, low-carbohydrate and high-carbohydrate/high-fat diets and provide those mice and their tissues to the research projects in order to assess age-related metabolic consequences and clinical and anatomic pathologies. All mice analyzed will be on a congenic C57BL/6J genetic background and maintained in a mouse dedicated vivarium under barrier conditions. Core B will accomplish these objectives using relevant resources and technical expertise drawn primarily from the UC Davis Mouse Biology Program. Core B will fulfill the following two Specific Aims:
Specific Aim 1 : Provide p66Shc-/- and littermate control mice at selected stages of life ("cross-section analysis") in response to caloric restriction diet. p66Shc-/- and wild-type control mice will be bred, and sampled at specific intervals for biochemical and microarray analysis in Projects 1 and 2. The results of this Aim will reveal the extent to which She alters the metabolic response to sustained caloric restriction.
Specific Aim 2 : Provide p66Shc-/- and littermate control mice for lifespan analysis and assess clinical and anatomic pathologies in response to high-fat/high-carbohydrate and low-carbohydrate diets. Similarly, p66Shc-/- mice resist high-fat diets and are expected to have increased lifespan in that condition, and so an investigation of lifespan-limiting pathology in that condition is important.
Aim 2 will serve the hypothesis that a low-carbohydrate thus the underlying diet mimics the effects of caloric restriction and She-deficiency extends lifespan, and pathology will be investigated.

Public Health Relevance

Obesity and diabetes are massive problems for Westerners who live in a high-fat diet environment. The program project has shown that She knockout mice resist both obesity and diabetes, and, as an animal core, Core B provides highly standardized, genetically characterized and clean mice for further studies of mechanism, and interventions to promote healthy aging.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Program Projects (P01)
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Special Emphasis Panel (ZAG1-ZIJ-2)
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University of California Davis
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Granatiero, Veronica; Patron, Maria; Tosatto, Anna et al. (2014) The use of aequorin and its variants for Ca2+ measurements. Cold Spring Harb Protoc 2014:9-16
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Bock, Fabian; Shahzad, Khurrum; Wang, Hongjie et al. (2013) Activated protein C ameliorates diabetic nephropathy by epigenetically inhibiting the redox enzyme p66Shc. Proc Natl Acad Sci U S A 110:648-53
Chen, Yana; Hagopian, Kevork; Bibus, Douglas et al. (2013) The influence of dietary lipid composition on liver mitochondria from mice following 1 month of calorie restriction. Biosci Rep 33:83-95

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