The central focus of this project is to evaluate age-sensitive skeletal traits in the group of 600 genotyped female HET mice for studies of genetic linkage. We hypothesize that specific variation in the material or structural properties of bone will correlate to specific genotype data and thereby allow for the identification of marker loci that co- segregate with these specific skeletal traits of interest. The study will involve the measuring of biomechanical, architectural and compositional properties of cortical and trabecular bone taken from the femurs and vertebral bodies of the mice. The studies will be hierarchically based beginning with whole bone femurs and vertebral bodies of the mice. The studies will be hierarchically based beginning with whole bone biomechanical properties and 3-dimensional architectural measures using micro computed tomography and progressing towards the machining and testing of microbeam specimens (100 micron parallelopiped beams) which will provide estimates of properties of the tissue extracellular matrix. The hierarchical based characterizations of skeletal fragility will be measured on all mice and then further evaluated for a genetically selected population of mice chosen on the basis of their alleles at """"""""longevity associated"""""""" loci. Results of these studies will not only provide genotypic correlations to features of skeletal fragility but will also provide insight into the mechanisms associated with maintaining skeletal mechanical integrity. We will also be able to draw correlations between bone specific traits and changes in other multiple organ systems being evaluated in the whole program.
| 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 |
| Bennett-Baker, Pamela E; Wilkowski, Jodi; Burke, David T (2003) Age-associated activation of epigenetically repressed genes in the mouse. Genetics 165:2055-62 |
| Volkman, Suzanne K; Galecki, Andrzej T; Burke, David T et al. (2003) Quantitative trait loci for femoral size and shape in a genetically heterogeneous mouse population. J Bone Miner Res 18:1497-505 |
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