Genetics of Bone Mineralization and Morphology in Inbred Mice: Analysis of the HcB/Dem Recombinant Congenic Strains.

摘要

Susceptibility to osteoporotic fractures varies widely with genetic factors accounting for approximately (caret)50% of this variation. Fracture risk is determined by peak bone mass and skeletal morphology achieved in young adulthood and the rate and extent of bone loss thereafter. This work will analyze the genetics of the first of these components through the use of recombinant congenic mice. We have demonstrated that the 27 HcB/Dem strains differ significantly in a variety of bone strength related phenotypes at 6 months of age. Further, preliminary mapping of genetic loci contributing to these phenotypes has been carried out. An intercross between HcB/13 and HcB/14 will allow more accurate mapping of a subset of these bone strength genes and investigation into pairwise epistatic interactions among loci. A cross examining Cola2(sup oim)/+ heterozygotes will allow determination of whether segregating differential loci in this system map to the same chromosomal regions identified in the HcB/Dem studies. Further breeding will be performed to develop true congenic lines and refine the mapping of the candidate genes for their positional cloning. 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.