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Mouse mutant phenotyping at scale reveals novel genes controlling bone mineral density


The genetic landscape of diseases associated with changes in bone mineral density (BMD), such as osteoporosis, is only partially understood. Here, we explored data from 3,823 mutant mouse strains for BMD, a measure that is frequently altered in a range of bone pathologies, including osteoporosis. A total of 200 genes were found to significantly affect BMD. This pool of BMD genes comprised 141 genes with previously unknown functions in bone biology and was complementary to pools derived from recent human studies. Nineteen of the 141 genes also caused skeletal abnormalities. Examination of the BMD genes in osteoclasts and osteoblasts underscored BMD pathways, including vesicle transport, in these cells and together with in silico bone turnover studies resulted in the prioritization of candidate genes for further investigation. Overall, the results add novel pathophysiological and molecular insight into bone health and disease.

Type Journal
ISBN 1553-7404 (Electronic) 1553-7390 (Linking)
Authors Swan, A. L.; Schutt, C.; Rozman, J.; Del Mar Muniz Moreno, M.; Brandmaier, S.; Simon, M.; Leuchtenberger, S.; Griffiths, M.; Brommage, R.; Keskivali-Bond, P.; Grallert, H.; Werner, T.; Teperino, R.; Becker, L.; Miller, G.; Moshiri, A.; Seavitt, J. R.; Cissell, D. D.; Meehan, T. F.; Acar, E. F.; Lelliott, C. J.; Flenniken, A. M.; Champy, M. F.; Sorg, T.; Ayadi, A.; Braun, R. E.; Cater, H.; Dickinson, M. E.; Flicek, P.; Gallegos, J.; Ghirardello, E. J.; Heaney, J. D.; Jacquot, S.; Lally, C.; Logan, J. G.; Teboul, L.; Mason, J.; Spielmann, N.; McKerlie, C.; Murray, S. A.; Nutter, L. M. J.; Odfalk, K. F.; Parkinson, H.; Prochazka, J.; Reynolds, C. L.; Selloum, M.; Spoutil, F.; Svenson, K. L.; Vales, T. S.; Wells, S. E.; White, J. K.; Sedlacek, R.; Wurst, W.; Lloyd, K. C. K.; Croucher, P. I.; Fuchs, H.; Williams, G. R.; Bassett, J. H. D.; Gailus-Durner, V.; Herault, Y.; Mallon, A. M.; Brown, S. D. M.; Mayer-Kuckuk, P.; Hrabe de Angelis, M.; Consortium, Impc
Responsible Garvan Author Prof Peter Croucher
Publisher Name PLOS GENET
Published Date 2020-12-28
Published Volume 16
Published Issue 12
Published Pages e1009190
Status Published in-print
DOI 10.1371/journal.pgen.1009190
URL link to publisher's version