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.
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