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.
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.
| Roberts, Megan N; Wallace, Marita A; Tomilov, Alexey A et al. (2018) A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice. Cell Metab 27:1156 |
| Penna, Elisa; Espino, Javier; De Stefani, Diego et al. (2018) The MCU complex in cell death. Cell Calcium 69:73-80 |
| Pallafacchina, Giorgia; Zanin, Sofia; Rizzuto, Rosario (2018) Recent advances in the molecular mechanism of mitochondrial calcium uptake. F1000Res 7: |
| McMackin, Marissa Z; Henderson, Chelsea K; Cortopassi, Gino A (2017) Neurobehavioral deficits in the KIKO mouse model of Friedreich's ataxia. Behav Brain Res 316:183-188 |
| Taylor, Sandra L; Ruhaak, L Renee; Kelly, Karen et al. (2017) Effects of imputation on correlation: implications for analysis of mass spectrometry data from multiple biological matrices. Brief Bioinform 18:312-320 |
| Jasoliya, Mittal J; McMackin, Marissa Z; Henderson, Chelsea K et al. (2017) Frataxin deficiency impairs mitochondrial biogenesis in cells, mice and humans. Hum Mol Genet 26:2627-2633 |
| Song, Lanying; Yu, Alfred; Murray, Karl et al. (2017) Bipolar cell reduction precedes retinal ganglion neuron loss in a complex 1 knockout mouse model. Brain Res 1657:232-244 |
| Roberts, Megan N; Wallace, Marita A; Tomilov, Alexey A et al. (2017) A Ketogenic Diet Extends Longevity and Healthspan in Adult Mice. Cell Metab 26:539-546.e5 |
| Taylor, Sandra L; Ruhaak, L Renee; Weiss, Robert H et al. (2017) Multivariate two-part statistics for analysis of correlated mass spectrometry data from multiple biological specimens. Bioinformatics 33:17-25 |
| Hayashi, Genki; Jasoliya, Mittal; Sahdeo, Sunil et al. (2017) Dimethyl fumarate mediates Nrf2-dependent mitochondrial biogenesis in mice and humans. Hum Mol Genet 26:2864-2873 |
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