Mouse mutant phenotyping at scale reveals novel genes controlling bone mineral density
In: PLoS Genetics PLoS Genetics, Public Library of Science, 2020, 16 (12), pp.e1009190. ⟨10.1371/journal.pgen.1009190⟩ PLoS genetics, vol 16, iss 12 PLoS Genet. 16:e1009190 (2021) PLoS Genetics 16(12), Jg. 16 (2021-02-09), Heft 12, p e1009190
Online
unknown
Zugriff:
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.
Author summary Patients affected by osteoporosis frequently present with decreased BMD and increased fracture risk. Genes are known to control the onset and progression of bone diseases such as osteoporosis. Therefore, we aimed to identify osteoporosis-related genes using BMD measures obtained from a large pool of mutant mice genetically modified for deletion of individual genes (knockout mice). In a collaborative endeavor involving several research sites world-wide, we generated and phenotyped 3,823 knockout mice and identified 200 genes which regulated BMD. Of the 200 BMD genes, 141 genes were previously not known to affect BMD. The discovery and study of novel BMD genes will help to better understand the causes and therapeutic options for patients with low BMD. In the long run, this will improve the clinical management of osteoporosis.
| Titel: |
Mouse mutant phenotyping at scale reveals novel genes controlling bone mineral density
|
|---|---|
| Autor/in / Beteiligte Person: | Flicek, Paul ; Teperino, Raffaele ; Teboul, Lydia ; Werner, Thomas ; Champy, Marie-France ; Lelliott, Christopher J. ; Williams, Graham R. ; White, Jacqueline K. ; Miller, Gregor ; Dickinson, Mary E. ; Ann M Flenniken ; Sedlacek, Radislav ; Martin Hrabé de Angelis ; Seavitt, John R. ; Croucher, Peter I. ; Maria del Mar Muniz Moreno ; Wells, Sara ; Rozman, Jan ; Meehan, Terrence F. ; Kristian F Odfalk ; Gallegos, Juan ; J. H. Duncan Bassett ; Selloum, Mohammed ; Logan, John G. ; Jacquot, Sylvie ; Ghirardello, Elena J. ; Braun, Robert ; Spoutil, Frantisek ; Kevin C K Lloyd ; Becker, Lore ; Murray, Stephen A. ; Prochazka, Jan ; Acar, Elif F. ; Taylor S Vales ; Simon, Michelle ; Fuchs, Helmut ; Spielmann, Nadine ; Griffiths, Mark ; Keskivali-Bond, Piia ; Gailus-Durner, Valerie ; Sorg, Tania ; Schütt, Christine ; Mason, Jeremy ; Parkinson, Helen ; Svenson, Karen L. ; Ayadi, Abdel ; Anna L Swan ; Heaney, Jason D. ; McKerlie, Colin ; Wurst, Wolfgang ; Mallon, Ann-Marie ; Cater, Heather ; Leuchtenberger, Stefanie ; Grallert, Harald ; Steve D.M. Brown ; Brandmaier, Stefan ; Herault, Yann ; Mayer-Kuckuk, Philipp ; Reynolds, Corey L. ; Moshiri, Ala ; Brommage, Robert ; Cissell, Derek D. ; Lauryl M J Nutter ; Lally, Connor ; MRC Harwell Institute [UK] ; German Research Center for Environmental Health - Helmholtz Center München (GmbH) ; German Center for Diabetes Research - Deutsches Zentrum für Diabetesforschung [Neuherberg] (DZD) ; Institute of Molecular Genetics of the Czech Academy of Sciences (IMG / CAS) ; Czech Academy of Sciences [Prague] (CAS) ; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC) ; Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) ; Helmholtz-Zentrum München (HZM) ; The Wellcome Trust Sanger Institute [Cambridge] ; University of Michigan [Ann Arbor] ; University of Michigan System ; University of California [Davis] (UC Davis) ; University of California ; Baylor College of Medicine (BCM) ; University, Baylor ; European Molecular Biology Laboratory [Hinxton] ; University of Toronto ; University of Manitoba [Winnipeg] ; Lunenfeld-Tanenbaum Research Institute [Toronto, Canada] ; French National Infrastructure for Mouse Phenogenomics (PHENOMIN) ; The Jackson Laboratory [Bar Harbor] (JAX) ; European Bioinformatics Institute [Hinxton] (EMBL-EBI) ; Heidelberg, EMBL ; Imperial College London ; Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM) ; Deutsches Zentrum für Neurodegenerative Erkrankungen [Ulm] (DZNE) ; German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) ; Munich Cluster for systems neurology [Munich] (SyNergy) ; Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Ludwig-Maximilians-Universität München (LMU) ; Garvan Institute of Medical Research [Sydney, Australia] ; St. Vincent’s Clinical School [Sydney, Australia] ; UNSW Faculty of Medicine [Sydney] ; University of New South Wales [Sydney] (UNSW)-University of New South Wales [Sydney] (UNSW) ; Université de Nouvelle-Galles du Sud - UNSW [Sydney, Australia] ; Mundlos, Stefan ; Trust, Wellcome ; Commission of the European Communities ; Commission, European ; Helmholtz Zentrum München = German Research Center for Environmental Health ; University of California (UC) ; Garvan Institute of medical research ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA) ; Technische Universität München [München] (TUM) ; Technische Universität München [München] (TUM)-Ludwig-Maximilians-Universität München (LMU) ; Swan, Anna L [0000-0003-1810-3756] ; Rozman, Jan [0000-0002-8035-8904] ; Del Mar Muñiz Moreno, Maria [0000-0002-2662-890X] ; Leuchtenberger, Stefanie [0000-0003-2475-0810] ; Brommage, Robert [0000-0002-9947-3822] ; Grallert, Harald [0000-0002-6876-9655] ; Werner, Thomas [0000-0003-0402-4539] ; Teperino, Raffaele [0000-0001-8815-1409] ; Becker, Lore [0000-0002-6890-4984] ; Miller, Gregor [0000-0002-4281-4905] ; Seavitt, John R [0000-0003-3209-3187] ; Cissell, Derek D [0000-0002-6450-422X] ; Acar, Elif F [0000-0003-2908-7691] ; Lelliott, Christopher J [0000-0001-8087-4530] ; Braun, Robert E [0000-0003-3856-9465] ; Cater, Heather [0000-0002-8696-6070] ; Flicek, Paul [0000-0002-3897-7955] ; Ghirardello, Elena J [0000-0002-1100-9217] ; Heaney, Jason D [0000-0001-8475-8828] ; Lally, Connor [0000-0002-3801-1966] ; Logan, John G [0000-0003-2801-700X] ; Mason, Jeremy [0000-0002-2796-5123] ; Nutter, Lauryl MJ [0000-0001-9619-146X] ; Odfalk, Kristian F [0000-0003-4152-4583] ; Prochazka, Jan [0000-0003-4675-8995] ; Selloum, Mohammed [0000-0003-4057-3519] ; Spoutil, Frantisek [0000-0002-7310-3487] ; Svenson, Karen L [0000-0002-7928-1911] ; Vales, Taylor S [0000-0001-9751-5681] ; Wells, Sara E [0000-0002-0572-0600] ; White, Jacqueline K [0000-0001-6268-2826] ; Sedlacek, Radislav [0000-0002-3352-392X] ; Wurst, Wolfgang [0000-0003-4422-7410] ; Lloyd, KC Kent [0000-0002-5318-4144] ; Williams, Graham R [0000-0002-8555-8219] ; Herault, Yann [0000-0001-7049-6900] ; Brown, Steve DM [0000-0002-0617-4824] ; Hrabe de Angelis, Martin [0000-0002-7898-2353] ; Apollo - University of Cambridge Repository |
| Link: | |
| Zeitschrift: | PLoS Genetics PLoS Genetics, Public Library of Science, 2020, 16 (12), pp.e1009190. ⟨10.1371/journal.pgen.1009190⟩ PLoS genetics, vol 16, iss 12 PLoS Genet. 16:e1009190 (2021) PLoS Genetics 16(12), Jg. 16 (2021-02-09), Heft 12, p e1009190 |
| Veröffentlichung: | Public Library of Science (PLoS), 2021 |
| Medientyp: | unknown |
| ISSN: | 1553-7390 (print) ; 1553-7404 (print) |
| DOI: | 10.17863/cam.64423 |
| Schlagwort: |
|
| Sonstiges: |
|