Document Type
Article
Publication Date
12-28-2020
Keywords
JMG
JAX Source
PLoS Genet 2020 Dec 28; 16(12):e1009190
Volume
16
Issue
12
First Page
1009190
Last Page
1009190
ISSN
1553-7404
PMID
33370286
DOI
https://doi.org/10.1371/journal.pgen.1009190
Grant
DO023222
Abstract
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.
Recommended Citation
Swan A,
Schütt C,
Rozman J,
Del Mar Muñiz 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,
Cissell D,
Meehan T,
Acar E,
Lelliott C,
Flenniken A,
Champy M,
Sorg T,
Ayadi A,
Braun R,
Cater H,
Dickinson M,
Flicek P,
Gallegos J,
Ghirardello E,
Heaney J,
Jacquot S,
Lally C,
Logan J,
Teboul L,
Mason J,
Spielmann N,
McKerlie C,
Murray SA,
Nutter L,
Odfalk K,
Parkinson H,
Prochazka J,
Reynolds C,
Selloum M,
Spoutil F,
Svenson KL,
Vales T,
Wells S,
White J,
Sedlacek R,
Wurst W,
Lloyd K,
Croucher P,
Fuchs H,
Williams G,
Bassett D,
Gailus-Durner V,
Herault Y,
Mallon A,
Brown S,
Mayer-Kuckuk P,
Hrabe de Angelis M,
Consortium I.
Mouse mutant phenotyping at scale reveals novel genes controlling bone mineral density. PLoS Genet 2020 Dec 28; 16(12):e1009190
Comments
REB, SAM, JKW, KLS thank the members of the Jackson Laboratory Research Animal Facility and Laboratory Informatics Team for their outstanding support.
This is an open access article distributed under the terms of theCreative Commons Attribution License.