Genetics of Bone Mineralization and Morphology in Inbred Mice: Analysis of the HcB/Dem Recombinant Congenic Strains
Final rept. 1 Apr 2000-31 Mar 2005
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This work will analyze the genetics of the first of these components through the use of recombinant congenic mice. We performed an intercross between HcB13 and HcBl4. Broad-sense heritability of failure load is approximately 0.5, matching the expectation based on epidemiology. Linkage mapping in this cross will allow more accurate mapping of a subset of these bone strength genes and investigation into pairwise epistatic interactions among loci. Further breeding will be performed to develop true congenic lines and refine the mapping of the candidate genes for their positional cloning. A cross examining Colla2oim heterozygotes has identified several bone strength modifying loci. Interestingly, these largely overlap quantitative trait loci found to affect bone mineral density and bone size in wild-type mice. Additional work in this system has identified a dental phenotype in both homozygotes and heterozygotes harboring the Colla2oim mutation. Nanoindentation testing, including compliance analysis has allowed determinabon of Youngs modulus and Meyer hardness independent of sample geometry. Identifying mouse chromosome regions that control peak bone mineralization and morphology will allow prediction of the corresponding human regions by synteny and facilitate human genetic studies of this problem.
- Medicine and Medical Research