BoneKEy Reports | BoneKEy Watch

Using mice strains to identify new genes associated with osteoporosis



DOI:10.1038/bonekey.2013.121

In order to identify quantitative trait loci (QTLs) associated with six skeletal traits, including three connected with bone mineral density (BMD), Leamy et al. devised a complex series of experiments. These were performed in strains of mice produced by crossing mice that showed a predisposition to obesity when fed a high-fat diet with mice prone to a high rate of wheel running. The researchers fed mice either a diet high in fat or a matched control diet so they could identify QTLs for different skeletal traits that had an interaction with diet.

In total, they identified 50 QTLs, which represented 32 individual genomic sites that impacted on the six skeletal traits. These were different from the QTLs suggested by a genome scan of a previous generation of the same mouse intercross. Several of the QTLs with strong association with the BMD traits were located on chromosome 1. A possible candidate gene with a matching location is Cyp51; mice with a knockout of this gene show significant skeletal abnormalities.

Two of the QTLs showed interaction with a high-fat diet and the authors noted several QTLs that showed interactions with sex.

Editor’s comment: No reasonable candidate genes emerged for the QTLs associated with diet. It would be interesting to investigate if any of these QTLs showed interactions with physical activity.


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