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

Autor: Swan AL; MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus, Oxfordshire, United Kingdom., Schütt C; German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Neuherberg, Germany., Rozman J; German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Neuherberg, Germany.; German Center for Diabetes Research (DZD), Neuherberg, Germany.; Czech Center for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences,Vestec, Czech Republic., Del Mar Muñiz Moreno M; Université de Strasbourg, CNRS, INSERM, IGBMC, Illkirch, France., Brandmaier S; German Center for Diabetes Research (DZD), Neuherberg, Germany.; Research Unit of Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany., Simon M; MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus, Oxfordshire, United Kingdom., Leuchtenberger S; German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Neuherberg, Germany., Griffiths M; Mouse Informatics Group, Wellcome Sanger Institute, Hinxton, United Kingdom., Brommage R; German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Neuherberg, Germany., Keskivali-Bond P; MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus, Oxfordshire, United Kingdom., Grallert H; German Center for Diabetes Research (DZD), Neuherberg, Germany.; Research Unit of Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany., Werner T; Internal Medicine Nephrology and Center for Computational Medicine & Bioinformatics, University of Michigan, Ann Arbor, Michigan, United States of America., Teperino R; German Center for Diabetes Research (DZD), Neuherberg, Germany.; Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Neuherberg, Germany., Becker L; German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Neuherberg, Germany., Miller G; German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Neuherberg, Germany., Moshiri A; University of California-Davis School of Medicine, Sacramento, California, United States of America., Seavitt JR; Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America., Cissell DD; Department of Surgical & Radiological Sciences, University of California, Davis, California, United States of America., Meehan TF; European Molecular Biology Laboratory- European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, United Kingdom., Acar EF; The Center for Phenogenomics, Toronto, Ontario, Canada.; The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.; Department of Statistics, University of Manitoba, Winnipeg, Manitoba, Canada., Lelliott CJ; Mouse Pipelines, Wellcome Sanger Institute, Hinxton, United Kingdom., Flenniken AM; The Center for Phenogenomics, Toronto, Ontario, Canada.; Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada., Champy MF; Université de Strasbourg, CNRS, INSERM, IGBMC, PHENOMIN-ICS, Illkirch, France., Sorg T; Université de Strasbourg, CNRS, INSERM, IGBMC, PHENOMIN-ICS, Illkirch, France., Ayadi A; Université de Strasbourg, CNRS, INSERM, IGBMC, PHENOMIN-ICS, Illkirch, France., Braun RE; The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine, United States of America., Cater H; MRC Harwell Institute, Mary Lyon Centre, Harwell Campus, Oxfordshire, United Kingdom., Dickinson ME; Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America.; Departments of Molecular Physiology & Biophysics, Baylor College of Medicine, One Baylor Plaza, Houston,Texas, United States of America., Flicek P; European Molecular Biology Laboratory- European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, United Kingdom., Gallegos J; Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America.; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, United States of America., Ghirardello EJ; Molecular Endocrinology Laboratory, Department of Metabolism, Digestion and Reproduction, Imperial College London, Hammersmith Campus, London, United Kingdom., Heaney JD; Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America.; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, United States of America., Jacquot S; Université de Strasbourg, CNRS, INSERM, IGBMC, PHENOMIN-ICS, Illkirch, France., Lally C; MRC Harwell Institute, Mary Lyon Centre, Harwell Campus, Oxfordshire, United Kingdom., Logan JG; Molecular Endocrinology Laboratory, Department of Metabolism, Digestion and Reproduction, Imperial College London, Hammersmith Campus, London, United Kingdom., Teboul L; MRC Harwell Institute, Mary Lyon Centre, Harwell Campus, Oxfordshire, United Kingdom., Mason J; European Molecular Biology Laboratory- European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, United Kingdom., Spielmann N; German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Neuherberg, Germany., McKerlie C; The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada., Murray SA; The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine, United States of America., Nutter LMJ; The Center for Phenogenomics, Toronto, Ontario, Canada.; Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada., Odfalk KF; Advanced Technologies Cores, Baylor College of Medicine, One Baylor Plaza, Houston Texas, United States of America., Parkinson H; European Molecular Biology Laboratory- European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, United Kingdom., Prochazka J; Czech Center for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences,Vestec, Czech Republic., Reynolds CL; Departments of Molecular Physiology & Biophysics, Baylor College of Medicine, One Baylor Plaza, Houston,Texas, United States of America., Selloum M; Université de Strasbourg, CNRS, INSERM, IGBMC, PHENOMIN-ICS, Illkirch, France., Spoutil F; Czech Center for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences,Vestec, Czech Republic., Svenson KL; The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine, United States of America., Vales TS; Advanced Technologies Cores, Baylor College of Medicine, One Baylor Plaza, Houston Texas, United States of America., Wells SE; MRC Harwell Institute, Mary Lyon Centre, Harwell Campus, Oxfordshire, United Kingdom., White JK; The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine, United States of America., Sedlacek R; Czech Center for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences,Vestec, Czech Republic., Wurst W; Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Neuherberg, Germany.; Chair of Developmental Genetics, TUM School of Life Sciences (SoLS), Technische Universität München, Freising, Germany.; Deutsches Institut für Neurodegenerative Erkrankungen (DZNE) Site Munich, Munich, Germany.; Munich Cluster for Systems Neurology (SyNergy), Adolf-Butenandt-Institut, Ludwig-Maximilians-Universität München, Munich, Germany., Lloyd KCK; Department of Surgery, School of Medicine and Mouse Biology Program, University of California Davis., Croucher PI; Garvan Institute of Medical Research, Sydney, New South Wales, Australia.; St Vincent's Clinical School, Faculty of Medicine, Sydney, New South Wales, Australia.; School of Biotechnology and Biomolecular Sciences, UNSW Australia, Sydney, New South Wales, Australia., Fuchs H; German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Neuherberg, Germany., Williams GR; Molecular Endocrinology Laboratory, Department of Metabolism, Digestion and Reproduction, Imperial College London, Hammersmith Campus, London, United Kingdom., Bassett JHD; Molecular Endocrinology Laboratory, Department of Metabolism, Digestion and Reproduction, Imperial College London, Hammersmith Campus, London, United Kingdom., Gailus-Durner V; German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Neuherberg, Germany., Herault Y; Université de Strasbourg, CNRS, INSERM, IGBMC, Illkirch, France.; Université de Strasbourg, CNRS, INSERM, IGBMC, PHENOMIN-ICS, Illkirch, France., Mallon AM; MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus, Oxfordshire, United Kingdom., Brown SDM; MRC Harwell Institute, Mammalian Genetics Unit, Harwell Campus, Oxfordshire, United Kingdom., Mayer-Kuckuk P; German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Neuherberg, Germany., Hrabe de Angelis M; German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Neuherberg, Germany.; German Center for Diabetes Research (DZD), Neuherberg, Germany.; Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Neuherberg, Germany.; Chair of Experimental Genetics, TUM School of Life Sciences (SoLS), Technische Universität München, Freising, Germany.
Jazyk: angličtina
Zdroj: PLoS genetics [PLoS Genet] 2020 Dec 28; Vol. 16 (12), pp. e1009190. Date of Electronic Publication: 2020 Dec 28 (Print Publication: 2020).
DOI: 10.1371/journal.pgen.1009190
Abstrakt: 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.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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