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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
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.
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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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