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

0539808 - ÚMG 2021 RIV US eng J - Journal Article
Swan, A.L. - Rozman, Jan - Procházka, Jan - Špoutil, František - Sedláček, Radislav … Total 65 authors
Mouse mutant phenotyping at scale reveals novel genes controlling bone mineral density.
PLoS Genetics. Roč. 16, č. 12 (2020), č. článku e1009190. ISSN 1553-7404. E-ISSN 1553-7404
R&D Projects: GA MŠMT(CZ) LM2015040; GA MŠMT(CZ) LM2018126; GA MŠMT(CZ) ED1.1.00/02.0109; GA MŠMT ED2.1.00/19.0395; GA MŠMT EF16_013/0001789
Institutional support: RVO:68378050
Keywords : GENOME-WIDE ASSOCIATION * OSTEOGENESIS IMPERFECTA * ANIMAL-MODELS * SEX * COLLAGEN * DIFFERENTIATION * IDENTIFICATION * METAANALYSIS * DISCOVERY * MUTATION
OECD category: Technologies involving identifying the functioning of DNA, proteins and enzymes and how they influence the onset of disease and maintenance of well-being (gene-based diagnostics and therapeutic interventions (pharmacogenomics, gene-based therapeutics)
Impact factor: 5.917, year: 2020
Method of publishing: Open access
https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1009190

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.
Permanent Link: http://hdl.handle.net/11104/0317508