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

AL. Swan, C. Schütt, J. Rozman, M. Del Mar Muñiz Moreno, S. Brandmaier, M. Simon, S. Leuchtenberger, M. Griffiths, R. Brommage, P. Keskivali-Bond, H. Grallert, T. Werner, R. Teperino, L. Becker, G. Miller, A. Moshiri, JR. Seavitt, DD. Cissell,...

. 2020 ; 16 (12) : e1009190. [pub] 20201228

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc21011700

Grantová podpora
UM1 OD023222 NIH HHS - United States
110141/Z/15/Z Wellcome Trust - United Kingdom
UM1 OD023221 NIH HHS - United States
MC_U142684172 Medical Research Council - United Kingdom
UM1 HG006370 NHGRI NIH HHS - United States
MC_U142684171 Medical Research Council - United Kingdom
U54 HG006364 NHGRI NIH HHS - United States
UM1 HG006348 NHGRI NIH HHS - United States
U42 OD011175 NIH HHS - United States
Wellcome Trust - United Kingdom
MC_A410 Medical Research Council - United Kingdom
101123 Wellcome Trust - United Kingdom

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.

Advanced Technologies Cores Baylor College of Medicine One Baylor Plaza Houston Texas United States of America

Chair of Developmental Genetics TUM School of Life Sciences Technische Universität München Freising Germany

Chair of Experimental Genetics TUM School of Life Sciences Technische Universität München Freising Germany

Czech Center for Phenogenomics Institute of Molecular Genetics of the Czech Academy of Sciences Vestec Czech Republic

Dan L Duncan Comprehensive Cancer Center Baylor College of Medicine One Baylor Plaza Houston Texas United States of America

Department of Statistics University of Manitoba Winnipeg Manitoba Canada

Department of Surgery School of Medicine and Mouse Biology Program University of California Davis

Department of Surgical and Radiological Sciences University of California Davis California United States of America

Departments of Molecular Physiology and Biophysics Baylor College of Medicine One Baylor Plaza Houston Texas United States of America

Deutsches Institut für Neurodegenerative Erkrankungen Site Munich Munich Germany

European Molecular Biology Laboratory European Bioinformatics Institute Wellcome Genome Campus Hinxton United Kingdom

Garvan Institute of Medical Research Sydney New South Wales Australia

German Center for Diabetes Research Neuherberg Germany

German Mouse Clinic Institute of Experimental Genetics Helmholtz Zentrum München German Research Center for Environmental Health GmbH Neuherberg Germany

Institute of Developmental Genetics Helmholtz Zentrum München German Research Center for Environmental Health GmbH Neuherberg Germany

Institute of Experimental Genetics Helmholtz Zentrum München German Research Center for Environmental Health GmbH Neuherberg Germany

Internal Medicine Nephrology and Center for Computational Medicine and Bioinformatics University of Michigan Ann Arbor Michigan United States of America

Lunenfeld Tanenbaum Research Institute Sinai Health System Toronto Ontario Canada

Molecular and Human Genetics Baylor College of Medicine Houston Texas United States of America

Molecular Endocrinology Laboratory Department of Metabolism Digestion and Reproduction Imperial College London Hammersmith Campus London United Kingdom

Mouse Informatics Group Wellcome Sanger Institute Hinxton United Kingdom

Mouse Pipelines Wellcome Sanger Institute Hinxton United Kingdom

MRC Harwell Institute Mammalian Genetics Unit Harwell Campus Oxfordshire United Kingdom

MRC Harwell Institute Mary Lyon Centre Harwell Campus Oxfordshire United Kingdom

Munich Cluster for Systems Neurology Adolf Butenandt Institut Ludwig Maximilians Universität München Munich Germany

Research Unit of Molecular Epidemiology Institute of Epidemiology Helmholtz Zentrum München Neuherberg Germany

School of Biotechnology and Biomolecular Sciences UNSW Australia Sydney New South Wales Australia

St Vincent's Clinical School Faculty of Medicine Sydney New South Wales Australia

The Center for Phenogenomics Toronto Ontario Canada

The Hospital for Sick Children University of Toronto Toronto Ontario Canada

The Jackson Laboratory 600 Main Street Bar Harbor Maine United States of America

Université de Strasbourg CNRS INSERM IGBMC Illkirch France

Université de Strasbourg CNRS INSERM IGBMC PHENOMIN ICS Illkirch France

University of California Davis School of Medicine Sacramento California United States of America

Citace poskytuje Crossref.org

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