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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG025532-07
Application #
8589538
Study Section
Special Emphasis Panel (ZAG1-ZIJ-2)
Project Start
Project End
Budget Start
2013-12-01
Budget End
2014-11-30
Support Year
7
Fiscal Year
2014
Total Cost
$100,529
Indirect Cost
$35,038
Name
University of California Davis
Department
Type
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
Tosatto, Anna; Sommaggio, Roberta; Kummerow, Carsten et al. (2016) The mitochondrial calcium uniporter regulates breast cancer progression via HIF-1α. EMBO Mol Med 8:569-85
Datta, Sandipan; Sahdeo, Sunil; Gray, Jennifer A et al. (2016) A high-throughput screen for mitochondrial function reveals known and novel mitochondrial toxicants in a library of environmental agents. Mitochondrion 31:79-83
Taylor, Sandra L; Ruhaak, L Renee; Kelly, Karen et al. (2016) Effects of imputation on correlation: implications for analysis of mass spectrometry data from multiple biological matrices. Brief Bioinform :
Tian, Jijing; Yang, Guoxiang; Chen, Huan-Yuan et al. (2016) Galectin-3 regulates inflammasome activation in cholestatic liver injury. FASEB J 30:4202-4213
Raffaello, Anna; Mammucari, Cristina; Gherardi, Gaia et al. (2016) Calcium at the Center of Cell Signaling: Interplay between Endoplasmic Reticulum, Mitochondria, and Lysosomes. Trends Biochem Sci 41:1035-1049
Tomilov, Alexey; Tomilova, Natalia; Shan, Yuxi et al. (2016) p46Shc Inhibits Thiolase and Lipid Oxidation in Mitochondria. J Biol Chem 291:12575-85
Datta, Sandipan; Tomilov, Alexey; Cortopassi, Gino (2016) Identification of small molecules that improve ATP synthesis defects conferred by Leber's hereditary optic neuropathy mutations. Mitochondrion 30:177-86
Shen, Yan; McMackin, Marissa Z; Shan, Yuxi et al. (2016) Frataxin Deficiency Promotes Excess Microglial DNA Damage and Inflammation that Is Rescued by PJ34. PLoS One 11:e0151026
Taylor, Sandra L; Ruhaak, L Renee; Weiss, Robert H et al. (2016) Multivariate two-part statistics for analysis of correlated mass spectrometry data from multiple biological specimens. Bioinformatics :
Song, Lanying; Cortopassi, Gino (2015) Mitochondrial complex I defects increase ubiquitin in substantia nigra. Brain Res 1594:82-91

Showing the most recent 10 out of 88 publications