Mouse mutant phenotyping at scale reveals novel genes controlling bone mineral density
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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822523/ https://www.ncbi.nlm.nih.gov/pubmed/33370286 http://dx.doi.org/10.1371/journal.pgen.1009190 |
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author | Swan, Anna L. Schütt, Christine Rozman, Jan del Mar Muñiz Moreno, Maria Brandmaier, Stefan Simon, Michelle Leuchtenberger, Stefanie Griffiths, Mark Brommage, Robert Keskivali-Bond, Piia Grallert, Harald Werner, Thomas Teperino, Raffaele Becker, Lore Miller, Gregor Moshiri, Ala Seavitt, John R. Cissell, Derek D. Meehan, Terrence F. Acar, Elif F. Lelliott, Christopher J. Flenniken, Ann M. Champy, Marie-France Sorg, Tania Ayadi, Abdel Braun, Robert E. Cater, Heather Dickinson, Mary E. Flicek, Paul Gallegos, Juan Ghirardello, Elena J. Heaney, Jason D. Jacquot, Sylvie Lally, Connor Logan, John G. Teboul, Lydia Mason, Jeremy Spielmann, Nadine McKerlie, Colin Murray, Stephen A. Nutter, Lauryl M. J. Odfalk, Kristian F. Parkinson, Helen Prochazka, Jan Reynolds, Corey L. Selloum, Mohammed Spoutil, Frantisek Svenson, Karen L. Vales, Taylor S. Wells, Sara E. White, Jacqueline K. Sedlacek, Radislav Wurst, Wolfgang Lloyd, K. C. Kent Croucher, Peter I. Fuchs, Helmut Williams, Graham R. Bassett, J. H. Duncan Gailus-Durner, Valerie Herault, Yann Mallon, Ann-Marie Brown, Steve D. M. Mayer-Kuckuk, Philipp Hrabe de Angelis, Martin |
author_facet | Swan, Anna L. Schütt, Christine Rozman, Jan del Mar Muñiz Moreno, Maria Brandmaier, Stefan Simon, Michelle Leuchtenberger, Stefanie Griffiths, Mark Brommage, Robert Keskivali-Bond, Piia Grallert, Harald Werner, Thomas Teperino, Raffaele Becker, Lore Miller, Gregor Moshiri, Ala Seavitt, John R. Cissell, Derek D. Meehan, Terrence F. Acar, Elif F. Lelliott, Christopher J. Flenniken, Ann M. Champy, Marie-France Sorg, Tania Ayadi, Abdel Braun, Robert E. Cater, Heather Dickinson, Mary E. Flicek, Paul Gallegos, Juan Ghirardello, Elena J. Heaney, Jason D. Jacquot, Sylvie Lally, Connor Logan, John G. Teboul, Lydia Mason, Jeremy Spielmann, Nadine McKerlie, Colin Murray, Stephen A. Nutter, Lauryl M. J. Odfalk, Kristian F. Parkinson, Helen Prochazka, Jan Reynolds, Corey L. Selloum, Mohammed Spoutil, Frantisek Svenson, Karen L. Vales, Taylor S. Wells, Sara E. White, Jacqueline K. Sedlacek, Radislav Wurst, Wolfgang Lloyd, K. C. Kent Croucher, Peter I. Fuchs, Helmut Williams, Graham R. Bassett, J. H. Duncan Gailus-Durner, Valerie Herault, Yann Mallon, Ann-Marie Brown, Steve D. M. Mayer-Kuckuk, Philipp Hrabe de Angelis, Martin |
author_sort | Swan, Anna L. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7822523 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-78225232021-02-01 Mouse mutant phenotyping at scale reveals novel genes controlling bone mineral density Swan, Anna L. Schütt, Christine Rozman, Jan del Mar Muñiz Moreno, Maria Brandmaier, Stefan Simon, Michelle Leuchtenberger, Stefanie Griffiths, Mark Brommage, Robert Keskivali-Bond, Piia Grallert, Harald Werner, Thomas Teperino, Raffaele Becker, Lore Miller, Gregor Moshiri, Ala Seavitt, John R. Cissell, Derek D. Meehan, Terrence F. Acar, Elif F. Lelliott, Christopher J. Flenniken, Ann M. Champy, Marie-France Sorg, Tania Ayadi, Abdel Braun, Robert E. Cater, Heather Dickinson, Mary E. Flicek, Paul Gallegos, Juan Ghirardello, Elena J. Heaney, Jason D. Jacquot, Sylvie Lally, Connor Logan, John G. Teboul, Lydia Mason, Jeremy Spielmann, Nadine McKerlie, Colin Murray, Stephen A. Nutter, Lauryl M. J. Odfalk, Kristian F. Parkinson, Helen Prochazka, Jan Reynolds, Corey L. Selloum, Mohammed Spoutil, Frantisek Svenson, Karen L. Vales, Taylor S. Wells, Sara E. White, Jacqueline K. Sedlacek, Radislav Wurst, Wolfgang Lloyd, K. C. Kent Croucher, Peter I. Fuchs, Helmut Williams, Graham R. Bassett, J. H. Duncan Gailus-Durner, Valerie Herault, Yann Mallon, Ann-Marie Brown, Steve D. M. Mayer-Kuckuk, Philipp Hrabe de Angelis, Martin PLoS Genet Research Article 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. Public Library of Science 2020-12-28 /pmc/articles/PMC7822523/ /pubmed/33370286 http://dx.doi.org/10.1371/journal.pgen.1009190 Text en © 2020 Swan et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Swan, Anna L. Schütt, Christine Rozman, Jan del Mar Muñiz Moreno, Maria Brandmaier, Stefan Simon, Michelle Leuchtenberger, Stefanie Griffiths, Mark Brommage, Robert Keskivali-Bond, Piia Grallert, Harald Werner, Thomas Teperino, Raffaele Becker, Lore Miller, Gregor Moshiri, Ala Seavitt, John R. Cissell, Derek D. Meehan, Terrence F. Acar, Elif F. Lelliott, Christopher J. Flenniken, Ann M. Champy, Marie-France Sorg, Tania Ayadi, Abdel Braun, Robert E. Cater, Heather Dickinson, Mary E. Flicek, Paul Gallegos, Juan Ghirardello, Elena J. Heaney, Jason D. Jacquot, Sylvie Lally, Connor Logan, John G. Teboul, Lydia Mason, Jeremy Spielmann, Nadine McKerlie, Colin Murray, Stephen A. Nutter, Lauryl M. J. Odfalk, Kristian F. Parkinson, Helen Prochazka, Jan Reynolds, Corey L. Selloum, Mohammed Spoutil, Frantisek Svenson, Karen L. Vales, Taylor S. Wells, Sara E. White, Jacqueline K. Sedlacek, Radislav Wurst, Wolfgang Lloyd, K. C. Kent Croucher, Peter I. Fuchs, Helmut Williams, Graham R. Bassett, J. H. Duncan Gailus-Durner, Valerie Herault, Yann Mallon, Ann-Marie Brown, Steve D. M. Mayer-Kuckuk, Philipp Hrabe de Angelis, Martin Mouse mutant phenotyping at scale reveals novel genes controlling bone mineral density |
title | Mouse mutant phenotyping at scale reveals novel genes controlling bone mineral density |
title_full | Mouse mutant phenotyping at scale reveals novel genes controlling bone mineral density |
title_fullStr | Mouse mutant phenotyping at scale reveals novel genes controlling bone mineral density |
title_full_unstemmed | Mouse mutant phenotyping at scale reveals novel genes controlling bone mineral density |
title_short | Mouse mutant phenotyping at scale reveals novel genes controlling bone mineral density |
title_sort | mouse mutant phenotyping at scale reveals novel genes controlling bone mineral density |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7822523/ https://www.ncbi.nlm.nih.gov/pubmed/33370286 http://dx.doi.org/10.1371/journal.pgen.1009190 |
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