{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T19:06:43Z","timestamp":1790795203093,"version":"4.1.0"},"reference-count":85,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,7,1]],"date-time":"2019-07-01T00:00:00Z","timestamp":1561939200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,7,1]],"date-time":"2019-07-01T00:00:00Z","timestamp":1561939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000065","name":"U.S. Department of Health &amp; Human Services | NIH | National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS102451"],"award-info":[{"award-number":["NS102451"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Gwendolyn Strong Foundation"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Spinal Muscular Atrophy (SMA) is a monogenic neurodegenerative disorder and the leading genetic cause of infantile mortality. While several functions have been ascribed to the SMN (survival motor neuron) protein, their specific contribution to the disease has yet to be fully elucidated. We hypothesized that some, but not all,\n                    <jats:italic>SMN<\/jats:italic>\n                    homologues would rescue the SMA phenotype in mouse models, thereby identifying disease-relevant domains. Using AAV9 to deliver Smn homologs to SMA mice, we identified a conservation threshold that marks the boundary at which homologs can rescue the SMA phenotype. Smn from\n                    <jats:italic>Danio rerio<\/jats:italic>\n                    and\n                    <jats:italic>Xenopus laevis<\/jats:italic>\n                    significantly prevent disease, whereas Smn from\n                    <jats:italic>Drosophila melanogaster<\/jats:italic>\n                    ,\n                    <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                    , and\n                    <jats:italic>Schizosaccharomyces pombe<\/jats:italic>\n                    was significantly less efficacious. This phenotypic rescue correlated with correction of RNA processing defects induced by SMN deficiency and neuromuscular junction pathology. Based upon the sequence conservation in the rescuing homologs, a minimal\n                    <jats:italic>SMN<\/jats:italic>\n                    construct was designed consisting of exons 2, 3, and 6, which showed a partial rescue of the SMA phenotype. While a significant extension in survival was observed, the absence of a complete rescue suggests that while the core conserved region is essential, additional sequences contribute to the overall ability of the SMN protein to rescue disease pathology.\n                  <\/jats:p>","DOI":"10.1038\/s41598-019-45822-8","type":"journal-article","created":{"date-parts":[[2019,7,1]],"date-time":"2019-07-01T06:03:09Z","timestamp":1561960989000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Functional characterization of SMN evolution in mouse models of SMA"],"prefix":"10.1038","volume":"9","author":[{"given":"Erkan Y.","family":"Osman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeline R.","family":"Bolding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Villal\u00f3n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin A.","family":"Kaifer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary C.","family":"Lorson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Tisdale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5065-8906","authenticated-orcid":false,"given":"Yue","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin C.","family":"Conant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9682-2639","authenticated-orcid":false,"given":"J. Chris","family":"Pires","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Livio","family":"Pellizzoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1023-2169","authenticated-orcid":false,"given":"Christian L.","family":"Lorson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,7,1]]},"reference":[{"key":"45822_CR1","unstructured":"Darras, B. T., Jones, H. R., Ryan, M. M. & De Vivo, D. C. Neuromuscular Disorders of Infancy, Childhood, and Adolescence: A Clinician\u2019s Approach. (Elsevier Science, 2014)."},{"key":"45822_CR2","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1136\/jmg.15.6.409","volume":"15","author":"J Pearn","year":"1978","unstructured":"Pearn, J. Incidence, prevalence, and gene frequency studies of chronic childhood spinal muscular atrophy. J. Med. Genet. 15, 409\u2013413 (1978).","journal-title":"J. Med. Genet."},{"key":"45822_CR3","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1016\/S0960-8966(97)00459-8","volume":"7","author":"K Zerres","year":"1997","unstructured":"Zerres, K., Wirth, B. & Rudnik-Schoneborn, S. Spinal muscular atrophy\u2013clinical and genetic correlations. Neuromuscular disorders: NMD 7, 202\u2013207 (1997).","journal-title":"Neuromuscular disorders: NMD"},{"key":"45822_CR4","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1001\/archneurol.2011.74","volume":"68","author":"SJ Kolb","year":"2011","unstructured":"Kolb, S. J. & Kissel, J. T. Spinal muscular atrophy: a timely review. Archives of neurology 68, 979\u2013984, https:\/\/doi.org\/10.1001\/archneurol.2011.74 (2011).","journal-title":"Archives of neurology"},{"key":"45822_CR5","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/0092-8674(95)90460-3","volume":"80","author":"S Lefebvre","year":"1995","unstructured":"Lefebvre, S. et al. Identification and characterization of a spinal muscular atrophy-determining gene. Cell 80, 155\u2013165 (1995).","journal-title":"Cell"},{"key":"45822_CR6","doi-asserted-by":"publisher","first-page":"6307","DOI":"10.1073\/pnas.96.11.6307","volume":"96","author":"CL Lorson","year":"1999","unstructured":"Lorson, C. L., Hahnen, E., Androphy, E. J. & Wirth, B. A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy. Proceedings of the National Academy of Sciences of the United States of America 96, 6307\u20136311 (1999).","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"45822_CR7","doi-asserted-by":"publisher","first-page":"1187","DOI":"10.1016\/j.celrep.2013.11.012","volume":"5","author":"S Tisdale","year":"2013","unstructured":"Tisdale, S. et al. SMN is essential for the biogenesis of U7 small nuclear ribonucleoprotein and 3\u2032-end formation of histone mRNAs. Cell reports 5, 1187\u20131195, https:\/\/doi.org\/10.1016\/j.celrep.2013.11.012 (2013).","journal-title":"Cell reports"},{"key":"45822_CR8","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.semcdb.2014.04.026","volume":"32","author":"DK Li","year":"2014","unstructured":"Li, D. K., Tisdale, S., Lotti, F. & Pellizzoni, L. SMN control of RNP assembly: from post-transcriptional gene regulation to motor neuron disease. 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