Mouse mutant phenotyping at scale reveals novel genes controlling bone mineral density.
Animals
Bone Density
/ genetics
Female
Gene Expression Regulation
/ genetics
Gene Ontology
Genetic Pleiotropy
Genome-Wide Association Study
Genotype
Male
Mice
Mice, Transgenic
Mutation
Osteoblasts
/ metabolism
Osteoclasts
/ metabolism
Osteoporosis
/ genetics
Phenotype
Promoter Regions, Genetic
Protein Interaction Maps
Sex Characteristics
Transcriptome
Journal
PLoS genetics
ISSN: 1553-7404
Titre abrégé: PLoS Genet
Pays: United States
ID NLM: 101239074
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
25
03
2020
accepted:
13
10
2020
revised:
22
01
2021
pubmed:
29
12
2020
medline:
30
3
2021
entrez:
28
12
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33370286
doi: 10.1371/journal.pgen.1009190
pii: PGENETICS-D-20-00438
pmc: PMC7822523
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1009190Subventions
Organisme : NEI NIH HHS
ID : K08 EY027463
Pays : United States
Organisme : NIH HHS
ID : UM1 OD023222
Pays : United States
Organisme : Wellcome Trust
ID : 101123
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 110141/Z/15/Z
Pays : United Kingdom
Organisme : NIH HHS
ID : UM1 OD023221
Pays : United States
Organisme : Medical Research Council
ID : MC_U142684171
Pays : United Kingdom
Organisme : NHGRI NIH HHS
ID : UM1 HG006370
Pays : United States
Organisme : Medical Research Council
ID : MC_A410
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : P30 CA034196
Pays : United States
Organisme : NHGRI NIH HHS
ID : U54 HG006364
Pays : United States
Organisme : Medical Research Council
ID : MC_U142684172
Pays : United Kingdom
Organisme : NHGRI NIH HHS
ID : UM1 HG006348
Pays : United States
Organisme : NIH HHS
ID : U42 OD011175
Pays : United States
Organisme : Wellcome Trust
Pays : United Kingdom
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Nat Genet. 2009 Nov;41(11):1199-206
pubmed: 19801982
EMBO J. 1997 Dec 15;16(24):7305-16
pubmed: 9405360
Lancet Diabetes Endocrinol. 2017 Nov;5(11):908-923
pubmed: 28689768
Biochem Biophys Res Commun. 2012 Feb 10;418(2):247-53
pubmed: 22252298
Nat Rev Genet. 2008 Dec;9(12):911-22
pubmed: 19002143
Calcif Tissue Int. 2018 Sep;103(3):353-358
pubmed: 29572562
Bone. 2007 Sep;41(3):340-5
pubmed: 17618849
Calcif Tissue Int. 2013 Oct;93(4):299-306
pubmed: 23183786
Biochim Biophys Acta Bioenerg. 2018 Nov;1859(11):1235-1248
pubmed: 30267671
Nat Commun. 2018 Jan 18;9(1):288
pubmed: 29348434
PLoS Genet. 2011 Apr;7(4):e1001372
pubmed: 21533022
Nature. 2015 Oct 1;526(7571):112-7
pubmed: 26367794
J Endocrinol. 2000 Aug;166(2):235-45
pubmed: 10927613
J Cell Biol. 2002 Oct 14;159(1):79-89
pubmed: 12379803
Sci Transl Med. 2020 Feb 5;12(529):
pubmed: 32024800
J Biol Chem. 2019 Feb 8;294(6):2133-2141
pubmed: 30541925
Nat Genet. 2015 Sep;47(9):969-978
pubmed: 26214591
Bone Res. 2014 Oct 28;2:14034
pubmed: 26273529
J Bone Miner Res. 2018 Jul;33(7):1260-1271
pubmed: 29669177
Orthop Res Rev. 2016 Sep 27;8:41-55
pubmed: 30774469
J Bone Miner Res. 2012 Oct;27(10):2051-64
pubmed: 22692763
J Bone Miner Res. 2007 Feb;22(2):173-183
pubmed: 17228994
J Med Genet. 1984 Aug;21(4):257-62
pubmed: 6492090
Nat Genet. 2017 Aug;49(8):1231-1238
pubmed: 28650483
Nat Commun. 2017 Jun 26;8:15475
pubmed: 28650954
Biomark Res. 2017 May 18;5:18
pubmed: 28529755
Nucleic Acids Res. 2015 Apr 20;43(7):e47
pubmed: 25605792
Traffic. 2012 Oct;13(10):1307-14
pubmed: 22759194
Nat Rev Genet. 2018 Jun;19(6):357-370
pubmed: 29626206
PLoS One. 2015 Jul 06;10(7):e0131274
pubmed: 26147094
Sci Rep. 2016 Jan 18;6:19470
pubmed: 26778110
Nat Genet. 2019 Feb;51(2):230-236
pubmed: 30664745
PLoS Genet. 2019 Feb 1;15(2):e1007917
pubmed: 30707697
J Bone Miner Res. 2007 Aug;22(8):1187-96
pubmed: 17451375
PLoS One. 2018 Jul 26;13(7):e0200785
pubmed: 30048462
Am J Hum Genet. 2018 Jan 4;102(1):88-102
pubmed: 29304378
Nature. 2016 Sep 22;537(7621):508-514
pubmed: 27626380
J Med Genet. 2001 Feb;38(2):132-6
pubmed: 11288717
Nat Rev Rheumatol. 2010 Feb;6(2):99-105
pubmed: 20125177
PLoS Genet. 2011 Aug;7(8):e1002254
pubmed: 21852963
J Musculoskelet Neuronal Interact. 2016 Jun 01;16(2):168-71
pubmed: 27282461
PLoS Genet. 2012;8(8):e1002858
pubmed: 22876197
Nat Rev Endocrinol. 2013 Oct;9(10):575-83
pubmed: 23938284
Bonekey Rep. 2016 May 18;5:802
pubmed: 27195109
Mol Biol Cell. 2002 Sep;13(9):3268-80
pubmed: 12221131
J Bone Miner Res. 2008 Sep;23(9):1353-68
pubmed: 18505374
Genes Dev. 2006 Sep 15;20(18):2492-506
pubmed: 16980579
Osteoporos Int. 2009 May;20 Suppl 3:S247-53
pubmed: 19430876
Anat Rec. 1989 Jun;224(2):123-38
pubmed: 2672880
Blood. 2013 Nov 28;122(23):3845-7
pubmed: 24288412
Mol Biol Cell. 2013 Aug;24(16):2570-81
pubmed: 23783033
Nat Commun. 2017 Oct 12;8(1):886
pubmed: 29026089
PLoS Genet. 2014 Jun 19;10(6):e1004423
pubmed: 24945404
N Engl J Med. 2016 May 26;374(21):2096-7
pubmed: 27223157
J Cell Biochem. 2005 Dec 1;96(5):927-37
pubmed: 16167328
Nat Genet. 2017 Oct;49(10):1468-1475
pubmed: 28869591
Biochem J. 2002 May 1;363(Pt 3):599-608
pubmed: 11964161
J Biol Chem. 2005 Jun 3;280(22):21162-8
pubmed: 15802266
J Bone Miner Res. 1995 Nov;10(11):1607-13
pubmed: 8592936
J Bone Miner Res. 2010 Feb;25(2):247-61
pubmed: 19594296
Nat Genet. 2019 Feb;51(2):258-266
pubmed: 30598549
J Bone Miner Res. 2008 Feb;23(2):247-52
pubmed: 17937535
Physiol Rev. 2017 Jan;97(1):135-187
pubmed: 27807202