BoneKEy Reports | BoneKEy Watch

Mouse phenotyping consortium identifies novel osteoporosis genes

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DOI:10.1038/bonekey.2012.214

Bassett et al. applied a high-throughput phenotype screen to 100 unselected knockout (KO) mice strains generated by the Wellcome Trust/Sanger Mouse Genetics Project, part of the International Mouse Phenotyping Consortium. The goal was to try to pinpoint novel genes involved in bone strength to further elucidate the genetic basis of osteoporosis. Individual mouse strains were characterized by integrating quantitative X-ray microradiography, micro-computed tomography and biomechanical testing.

This new technique represents an efficient and rapid functional screening approach for identifying genes involved in susceptibility to a range of complex diseases. This proof-of-principle study revealed ten genes that contribute to bone strength and structure but that had not been previously identified using other methods. Six of the initial 100 KO mouse strains with abnormally low bone mass had deletions in key genes (Bbx, Cadm1, Fam73b, Sparc, Prpsap2 and Slc38a10). Four other KO mouse strains with high bone mass had deletions in the genes Asxl1, Trim45, Spns2 and Setdb1.

Editor's comment: A close correlation was identified between functional defects and the genes identified—for example, Sparc KO mice had weak and brittle bones and low bone mineral content, and we know that Sparc codes for osteonectin, the extracellular matrix glycoprotein. However, as the tissue expression patterns of the targeted genes were measured in 6–12-week-old mice, some genes with late-life expression might be missed using this approach.

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