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Although neuromuscular pathology is the most severe feature of <jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content>, other organs and tissues, including the heart, are also known to be affected in both patients and animal models. Here, we provide new insights into changes occurring in the heart, predominantly at pre\u2010 and early symptomatic ages, in the Taiwanese mouse model of severe <jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content>. Thinning of the interventricular septum and dilation of the ventricles occurred at pre\u2010 and early symptomatic ages. However, the left ventricular wall was significantly thinner in <jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content> mice from birth, occurring prior to any overt neuromuscular symptoms. Alterations in collagen <jats:styled-content style=\"fixed-case\">IV<\/jats:styled-content> protein from birth indicated changes to the basement membrane and contributed to the abnormal arrangement of cardiomyocytes in <jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content> hearts. This raises the possibility that developmental defects, occurring prenatally, may contribute to cardiac pathology in <jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content>. In addition, cardiomyocytes in <jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content> hearts exhibited oxidative stress at pre\u2010symptomatic ages and increased apoptosis during early symptomatic stages of disease. Heart microvasculature was similarly decreased at an early symptomatic age, likely contributing to the oxidative stress and apoptosis phenotypes observed. Finally, an increased incidence of blood retention in <jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content> hearts post\u2010fixation suggests the likelihood of functional defects, resulting in blood pooling. These pathologies mirror dilated cardiomyopathy, with clear consequences for heart function that would likely contribute to potential heart failure. Our findings add significant additional experimental evidence in support of the requirement to develop systemic therapies for <jats:styled-content style=\"fixed-case\">SMA<\/jats:styled-content> capable of treating non\u2010neuromuscular pathologies.<\/jats:p>","DOI":"10.1111\/joa.12793","type":"journal-article","created":{"date-parts":[[2018,2,23]],"date-time":"2018-02-23T06:25:40Z","timestamp":1519367140000},"page":"965-978","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Developmental and degenerative cardiac defects in the Taiwanese mouse model of severe spinal muscular atrophy"],"prefix":"10.1111","volume":"232","author":[{"given":"Gillian K.","family":"Maxwell","sequence":"first","affiliation":[{"name":"Institute for Medical Science University of Aberdeen Aberdeen UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Szunyogova","sequence":"additional","affiliation":[{"name":"Institute for Medical Science University of Aberdeen Aberdeen UK"},{"name":"Euan MacDonald Centre for Motor Neurone Disease Research University of Edinburgh Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah K.","family":"Shorrock","sequence":"additional","affiliation":[{"name":"Euan MacDonald Centre for Motor Neurone Disease Research University of Edinburgh Edinburgh UK"},{"name":"Edinburgh Medical School: Biomedical Sciences University of Edinburgh Edinburgh 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":"Euan MacDonald Centre for Motor Neurone Disease Research University of Edinburgh Edinburgh UK"},{"name":"Edinburgh Medical School: Biomedical Sciences University of Edinburgh Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8848-8738","authenticated-orcid":false,"given":"Simon H.","family":"Parson","sequence":"additional","affiliation":[{"name":"Institute for Medical Science University of Aberdeen Aberdeen UK"},{"name":"Euan MacDonald Centre for Motor Neurone Disease Research University of Edinburgh Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,2,22]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.22106"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/08830738050200110301"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2009.01.071"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq300"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2012.238196"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1509758112"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23582"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu052"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006744"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3700670"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/7.4.528"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(95)92206-7"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/mtna.2016.47"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/hh1501.094115"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5273(89)90005-3"},{"key":"e_1_2_9_17_1","first-page":"119","article-title":"Type 1 spinal atrophy (Werdnig\u2010Hoffman disease). 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