The goal of Project 1 is to assess the immune status of the mice that form the focus of this Program Project, i.e. the 600 UM-HET3 mice in Population 1 and the 180 genotype-selected mice in Population 2. The test battery includes the following components: . Production of anti-erythrocyte antibodies at 4 and again at 15 months of age. . Quantitation of six T cell subsets (CD4 and CD8, CD4 and CD8 memory, and the CD4P and CD8P subsets that express cell surface P-glycoprotein) in blood and in spleen of mice at 18 months of age. . Tests of in vitro proliferation by cultured splenocytes activated by Con A or by anti-CD3 antibodies with or without anti-CD28 co- stimulation. In addition to providing assessments of immune phenotypes for tests of the three Program Aims shared by all of the projects, the data generated by Project 1 will provide answers to several questions about the relationships among T cell subsets, in vitro proliferation, and in vivo immunity in aging mice. These include; 1. Do age-sensitive T cell subset levels in peripheral blood provide a useful index of subset levels in internal lymphoid tissues? 2. Do the factors that lead to age-atypical values of any given T cell subset also regulate the levels of other age-sensitive subsets? For example, do middle-aged mice with high levels of CD4 memory cells, characteristic of advanced age, also exhibit relatively high levels of CD4M, CD4P, CD8P cells? 3. Do mice with relatively """"""""old"""""""" levels of T cell subsets show low levels of antibody production and poor responses in tests for in vitro proliferation? In conjunction with other Projects and Cores, these tests for immune status will provide a comprehensive picture of genetic effects on age- sensitive immune traits, and will help test the idea that the pace of immune change in adult life is regulated by factors that also time age- dependent changes in other physiological domains.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Program Projects (P01)
Project #
Application #
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Michigan Ann Arbor
Ann Arbor
United States
Zip Code
Burke, David T; Kozloff, Kenneth M; Chen, Shu et al. (2012) Dissection of complex adult traits in a mouse synthetic population. Genome Res 22:1549-57
Chisa, Jennifer L; Burke, David T (2007) Mammalian mRNA splice-isoform selection is tightly controlled. Genetics 175:1079-87
Hanlon, Philip; Lorenz, William Andrew; Shao, Zhihong et al. (2006) Three-locus and four-locus QTL interactions influence mouse insulin-like growth factor-I. Physiol Genomics 26:46-54
Harper, James M; Salmon, Adam B; Chang, Yayi et al. (2006) Stress resistance and aging: influence of genes and nutrition. Mech Ageing Dev 127:687-94
Harper, James M; Durkee, Stephen J; Smith-Wheelock, Michael et al. (2005) Hyperglycemia, impaired glucose tolerance and elevated glycated hemoglobin levels in a long-lived mouse stock. Exp Gerontol 40:303-14
Volkman, Suzanne K; Galecki, Andrzej T; Burke, David T et al. (2004) Quantitative trait loci that modulate femoral mechanical properties in a genetically heterogeneous mouse population. J Bone Miner Res 19:1497-505
Harper, James M; Galecki, Andrzej T; Burke, David T et al. (2004) Body weight, hormones and T cell subsets as predictors of life span in genetically heterogeneous mice. Mech Ageing Dev 125:381-90
Wisser, Kathleen C; Schauerte, Joseph A; Burke, David T et al. (2004) Mapping tissue-specific genes correlated with age-dependent changes in protein stability and function. Arch Biochem Biophys 432:58-70
Harper, James M; Galecki, Andrzej T; Burke, David T et al. (2003) Quantitative trait loci for insulin-like growth factor I, leptin, thyroxine, and corticosterone in genetically heterogeneous mice. Physiol Genomics 15:44-51
Bennett-Baker, Pamela E; Wilkowski, Jodi; Burke, David T (2003) Age-associated activation of epigenetically repressed genes in the mouse. Genetics 165:2055-62

Showing the most recent 10 out of 13 publications