{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T20:24:53Z","timestamp":1777580693565,"version":"3.51.4"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,5,24]],"date-time":"2019-05-24T00:00:00Z","timestamp":1558656000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,5,24]],"date-time":"2019-05-24T00:00:00Z","timestamp":1558656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000894","name":"Spinal Muscular Atrophy Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000894","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Spinal muscular atrophy (SMA) is caused by loss-of-function mutations in the survival of motoneuron gene 1 (<jats:italic>SMN1<\/jats:italic>). SMA is characterized by motoneuron death, skeletal muscle denervation and atrophy. Disease severity inversely correlates with copy number of a second gene (<jats:italic>SMN2<\/jats:italic>), which harbors a splicing defect that causes the production of inadequate levels of functional SMN protein. Small molecules that modify <jats:italic>SMN2<\/jats:italic> splicing towards increased production of functional SMN significantly ameliorate SMA phenotypes in mouse models of severe SMA. At suboptimal doses, splicing modifiers, such as SMN-C1, have served to generate mice that model milder SMA, referred to as pharmacological SMA mice, which survive into early adulthood. Nerve sprouting at endplates, known as terminal sprouting, is key to normal muscle fiber reinnervation following nerve injury and its promotion might mitigate neuromuscular symptoms in mild SMA. Sprouting has been difficult to study in severe SMA mice due to their short lifespan. Here, we show that pharmacological SMA mice are capable of terminal sprouting following reinnervation that is largely SMN-C1 dose-independent, but that they display a reinnervation delay that is critically SMN-C1 dose-dependent. Data also suggest that SMN-C1 can induce by itself a limited terminal sprouting response in SMA and wild-type normally-innervated endplates.<\/jats:p>","DOI":"10.1038\/s41598-019-44222-2","type":"journal-article","created":{"date-parts":[[2019,5,24]],"date-time":"2019-05-24T10:03:50Z","timestamp":1558692230000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Nerve sprouting capacity in a pharmacologically induced mouse model of spinal muscular atrophy"],"prefix":"10.1038","volume":"9","author":[{"given":"Mendell","family":"Rimer","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bonnie L.","family":"Seaberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pei-Fen","family":"Yen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven","family":"Lam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert Louis","family":"Hastings","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4993-9038","authenticated-orcid":false,"given":"Young il","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wesley J.","family":"Thompson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhihua","family":"Feng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Friedrich","family":"Metzger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergey","family":"Paushkin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chien-Ping","family":"Ko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,5,24]]},"reference":[{"key":"44222_CR1","unstructured":"Sumner, C. 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A single nucleotide difference that alters splicing patterns distinguishes the SMA gene SMN1 from the copy gene SMN2. Hum Mol Genet 8, 1177\u20131183 (1999).","journal-title":"Hum Mol Genet"},{"key":"44222_CR5","doi-asserted-by":"publisher","first-page":"6307","DOI":"10.1073\/pnas.96.11.6307","volume":"96","author":"C Lorson","year":"1999","unstructured":"Lorson, C., Hahnen, E., Androphy, E. & Wirth, B. A single nucleotide in the SMN gene regulates splicing and is reponsible for spinal muscular atrophy. Proc Natl Acad Sci USA 96, 6307\u20136311 (1999).","journal-title":"Proc Natl Acad Sci USA"},{"key":"44222_CR6","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1016\/j.gde.2013.03.003","volume":"23","author":"B Wirth","year":"2013","unstructured":"Wirth, B., Garbes, L. & Riessland, M. How genetic modifiers influence the phenotype of spinal muscular atrophy and suggest future therapeutic approaches. 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Hoffmann-La Roche. The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"7799"}}