{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T19:37:29Z","timestamp":1790537849346,"version":"4.1.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"16","license":[{"start":{"date-parts":[[2020,7,9]],"date-time":"2020-07-09T00:00:00Z","timestamp":1594252800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013428","name":"Stichting Spieren voor Spieren","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013428","id-type":"DOI","asserted-by":"publisher"}]},{"name":"BBSRC ISP"},{"name":"Euan MacDonald Centre"},{"name":"Doddie Weir Foundation"},{"name":"UK SMA Research Consortium"},{"name":"SMA Europe"},{"DOI":"10.13039\/501100000265","name":"MRC","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,9,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Spinal muscular atrophy (SMA) is a neuromuscular disease caused by mutations in survival motor neuron 1 (SMN1). SMN-restoring therapies have recently emerged; however, preclinical and clinical studies revealed a limited therapeutic time window and systemic aspects of the disease. This raises a fundamental question of whether SMA has presymptomatic, developmental components to disease pathogenesis. We have addressed this by combining micro-computed tomography (\u03bcCT) and comparative proteomics to examine systemic pre-symptomatic changes in a prenatal mouse model of SMA. Quantitative \u03bcCT analyses revealed that SMA embryos were significantly smaller than littermate controls, indicative of general developmental delay. More specifically, cardiac ventricles were smaller in SMA hearts, whilst liver and brain remained unaffected. In order to explore the molecular consequences of SMN depletion during development, we generated comprehensive, high-resolution, proteomic profiles of neuronal and non-neuronal organs in SMA mouse embryos. Significant molecular perturbations were observed in all organs examined, highlighting tissue-specific prenatal molecular phenotypes in SMA. Together, our data demonstrate considerable systemic changes at an early, presymptomatic stage in SMA mice, revealing a significant developmental component to SMA pathogenesis.<\/jats:p>","DOI":"10.1093\/hmg\/ddaa146","type":"journal-article","created":{"date-parts":[[2020,7,7]],"date-time":"2020-07-07T15:09:53Z","timestamp":1594134593000},"page":"2674-2683","source":"Crossref","is-referenced-by-count":46,"title":["Pre-natal manifestation of systemic developmental abnormalities in spinal muscular atrophy"],"prefix":"10.1093","volume":"29","author":[{"given":"Anna A L","family":"Motyl","sequence":"first","affiliation":[{"name":"Edinburgh Medical School: Biomedical Sciences, University of Edinburgh, Edinburgh EH8 9XD, UK"},{"name":"Euan MacDonald Centre for Motor Neurone Disease Research, University of Edinburgh, Edinburgh EH16 4SB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiterie M E","family":"Faller","sequence":"additional","affiliation":[{"name":"Royal (Dick) School of Veterinary Studies, University of Edinburgh, Edinburgh EH25 9RG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2330-9444","authenticated-orcid":false,"given":"Ewout J N","family":"Groen","sequence":"additional","affiliation":[{"name":"UMC Utrecht Brain Center, University Medical Center, Utrecht 3584 CG, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel A","family":"Kline","sequence":"additional","affiliation":[{"name":"Euan MacDonald Centre for Motor Neurone Disease Research, University of Edinburgh, Edinburgh EH16 4SB, UK"},{"name":"The Roslin Institute, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha L","family":"Eaton","sequence":"additional","affiliation":[{"name":"Euan MacDonald Centre for Motor Neurone Disease Research, University of Edinburgh, Edinburgh EH16 4SB, UK"},{"name":"The Roslin Institute, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leire M","family":"Ledahawsky","sequence":"additional","affiliation":[{"name":"Edinburgh Medical School: Biomedical Sciences, University of Edinburgh, Edinburgh EH8 9XD, UK"},{"name":"Euan MacDonald Centre for Motor Neurone Disease Research, University of Edinburgh, Edinburgh EH16 4SB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Chaytow","sequence":"additional","affiliation":[{"name":"Edinburgh Medical School: Biomedical Sciences, University of Edinburgh, Edinburgh EH8 9XD, UK"},{"name":"Euan MacDonald Centre for Motor Neurone Disease Research, University of Edinburgh, Edinburgh EH16 4SB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas J","family":"Lamont","sequence":"additional","affiliation":[{"name":"FingerPrints Proteomics Facility, University of Dundee, DD1 5EH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M","family":"Wishart","sequence":"additional","affiliation":[{"name":"Euan MacDonald Centre for Motor Neurone Disease Research, University of Edinburgh, Edinburgh EH16 4SB, UK"},{"name":"The Roslin Institute, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Ting","family":"Huang","sequence":"additional","affiliation":[{"name":"Edinburgh Medical School: Biomedical Sciences, University of Edinburgh, Edinburgh EH8 9XD, UK"},{"name":"Euan MacDonald Centre for Motor Neurone Disease Research, University of Edinburgh, Edinburgh EH16 4SB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0306-5577","authenticated-orcid":false,"given":"Thomas H","family":"Gillingwater","sequence":"additional","affiliation":[{"name":"Edinburgh Medical School: Biomedical Sciences, University of Edinburgh, Edinburgh EH8 9XD, UK"},{"name":"Euan MacDonald Centre for Motor Neurone Disease Research, University of Edinburgh, Edinburgh EH16 4SB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,7,9]]},"reference":[{"key":"2020110419215944200_ref1","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1136\/jmg.26.12.761","article-title":"A Hungarian study on Werdnig-Hoffmann disease","volume":"26","author":"Czeizel","year":"1989","journal-title":"J. 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Neurobiol."},{"key":"2020110419215944200_ref18","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1038\/nbt.1610","article-title":"Rescue of the spinal muscular atrophy phenotype in a mouse model by early postnatal delivery of SMN","volume":"28","author":"Foust","year":"2010","journal-title":"Nat. Biotechnol."},{"key":"2020110419215944200_ref19","doi-asserted-by":"crossref","first-page":"3029","DOI":"10.1172\/JCI57291","article-title":"Postsymptomatic restoration of SMN rescues the disease phenotype in a mouse model of severe spinal muscular atrophy","volume":"121","author":"Lutz","year":"2011","journal-title":"J. Clin. Invest."},{"key":"2020110419215944200_ref20","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1172\/JCI72017","article-title":"Requirement of enhanced survival Motoneuron protein imposed during neuromuscular junction maturation","volume":"124","author":"Kariya","year":"2014","journal-title":"J. Clin. 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