{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T02:51:55Z","timestamp":1791341515929,"version":"4.3.1"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T00:00:00Z","timestamp":1736899200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Biotechnology & Biological Council, including Institute Strategic Program","award":["BB\/X010945\/1"],"award-info":[{"award-number":["BB\/X010945\/1"]}]},{"DOI":"10.13039\/100007721","name":"Cure SMA","doi-asserted-by":"publisher","award":["MUR2021"],"award-info":[{"award-number":["MUR2021"]}],"id":[{"id":"10.13039\/100007721","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["IS3-R2.23"],"award-info":[{"award-number":["IS3-R2.23"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Tenovus Scotland","award":["E15\/4"],"award-info":[{"award-number":["E15\/4"]}]},{"DOI":"10.13039\/100005202","name":"Muscular Dystrophy Association","doi-asserted-by":"publisher","award":["417757"],"award-info":[{"award-number":["417757"]}],"id":[{"id":"10.13039\/100005202","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Spinal Muscular Atrophy is an autosomal dominant disease caused by mutations and deletions within the SMN1 gene, with predominantly childhood onset. Although primarily a motor neuron disease, defects in non-neuronal tissues are described in both patients and mouse models. Here, we have undertaken a detailed study of the heart in the Smn2B\/\u2212 mouse models of SMA, and reveal a thinning of the ventriclar walls as previously described in more severe mouse models of SMA. However most structural changes are resolved by accounting for the smaller body size of the SMA mouse, as was also confirmed in the SMN\u22067 model. Echocardiography revealed increased systolic function, which was particularly pronounced in subsets of mice and an increase in global longitudinal strain, collectively indicative of increased cardiac stress in the Smn2B\/\u2212 mouse model. We have used TMT proteomics to perform a longitudinal study of the proteome of the hearts of Smn2B\/\u2212 mice and reveal a progressive dysregulation of LXR\/RXR signalling which is a regulator of lipid metabolism. We further show consistent perturbations in lipid metabolism in the Smn2B\/\u2212, Smn\u2212\/\u2212;SMN2;Smn\u03947and Smn\u03947\/\u03947;SMN2 mouse models of SMA on the day of birth. This work indicates that although structural changes in the heart can be overstated by failing to account for body size, there are functional defects which could predispose the heart to subsequent failure. We identify a common molecular signature across mouse models pointing to a dysregulation in lipid metabolism, and suggest that manipulation of LXR\/RXR signalling offers an opportunity to impact upon these pathways.<\/jats:p>","DOI":"10.1093\/hmg\/ddaf006","type":"journal-article","created":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T07:15:15Z","timestamp":1736493315000},"page":"547-562","source":"Crossref","is-referenced-by-count":7,"title":["Alterations in cardiac function correlate with a disruption in fatty acid metabolism in a mouse model of SMA"],"prefix":"10.1093","volume":"34","author":[{"given":"Nithya N","family":"Nair","sequence":"first","affiliation":[{"name":"Centre for Discovery Brain Sciences, Hugh Robson Building, George Square, University of Edinburgh , Edinburgh EH8 9XD ,","place":["United Kingdom"]},{"name":"Euan McDonald Centre for Motor Neuron Disease Research, Hugh Robson Building, George Square, University of Edinburgh , Edinburgh EH8 9XD ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel A","family":"Kline","sequence":"additional","affiliation":[{"name":"Euan McDonald Centre for Motor Neuron Disease Research, Hugh Robson Building, George Square, University of Edinburgh , Edinburgh EH8 9XD ,","place":["United Kingdom"]},{"name":"The Roslin Institute, Royal (Dick) School of Veterinary Studies, The University of Edinburgh , Easter Bush Campus, Midlothian EH25 9RG ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imogen","family":"Boyd","sequence":"additional","affiliation":[{"name":"Centre for Discovery Brain Sciences, Hugh Robson Building, George Square, University of Edinburgh , Edinburgh EH8 9XD ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meenakshi","family":"Anikumar","sequence":"additional","affiliation":[{"name":"Centre for Discovery Brain Sciences, Hugh Robson Building, George Square, University of Edinburgh , Edinburgh EH8 9XD ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Thomson","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Science, The Queen's Medical Research Institute, 47 Little France Crescent, The University of Edinburgh , Edinburgh EH16 4TJ ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas J","family":"Lamont","sequence":"additional","affiliation":[{"name":"FingerPrints Proteomics Facility, School of Life Sciences, Dow Street, University of Dundee , Dundee DD1 5EH ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gillian A","family":"Gray","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Science, The Queen's Medical Research Institute, 47 Little France Crescent, The University of Edinburgh , Edinburgh EH16 4TJ ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M","family":"Wishart","sequence":"additional","affiliation":[{"name":"Euan McDonald Centre for Motor Neuron Disease Research, Hugh Robson Building, George Square, University of Edinburgh, Edinburgh EH8 9XD ,","place":["United Kingdom"]},{"name":"The Roslin Institute, Royal (Dick) School of Veterinary Studies, The University of Edinburgh , Easter Bush Campus, Midlothian EH25 9RG ,","place":["United Kingdom"]},{"name":"Centre for Systems Health and Integrated Metabolic Research, Clifton Boulevard, Nottingham Trent University , Nottingham NG1 4GG ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6841-702X","authenticated-orcid":false,"given":"Lyndsay M","family":"Murray","sequence":"additional","affiliation":[{"name":"Centre for Discovery Brain Sciences , Hugh Robson Building, George Square, University of Edinburgh, Edinburgh EH8 9XD ,","place":["United Kingdom"]},{"name":"Euan McDonald Centre for Motor Neuron Disease Research, Hugh Robson Building, George Square, University of Edinburgh, Edinburgh EH8 9XD ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,1,15]]},"reference":[{"key":"2025031012073067300_ref1","doi-asserted-by":"crossref","DOI":"10.3390\/cells11030417","article-title":"Restoring SMN expression: an overview of the therapeutic developments for the treatment of spinal muscular atrophy","volume":"11","author":"Aslesh","year":"2022","journal-title":"Cells"},{"key":"2025031012073067300_ref2","doi-asserted-by":"crossref","first-page":"24934","DOI":"10.52965\/001c.24934","article-title":"The antisense oligonucleotide Nusinersen for treatment of spinal muscular atrophy","volume":"13","author":"Edinoff","year":"2021","journal-title":"Orthop Rev 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