{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T03:10:35Z","timestamp":1791169835441,"version":"4.1.0"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Neurodegeneration"],"published-print":{"date-parts":[[2011,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Animal models of human diseases are essential as they allow analysis of the disease process at the cellular level and can advance therapeutics by serving as a tool for drug screening and target validation. Here we report the development of a complete genetic model of spinal muscular atrophy (SMA) in the vertebrate zebrafish to complement existing zebrafish, mouse, and invertebrate models and show its utility for testing compounds that alter\n                      <jats:italic>SMN2<\/jats:italic>\n                      splicing.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The human motoneuron disease SMA is caused by low levels, as opposed to a complete absence, of the survival motor neuron protein (SMN). To generate a true model of SMA in zebrafish, we have generated a transgenic zebrafish expressing the human\n                      <jats:italic>SMN2<\/jats:italic>\n                      gene (\n                      <jats:italic>hSMN2<\/jats:italic>\n                      ), which produces only a low amount of full-length SMN, and crossed this onto the\n                      <jats:italic>smn<\/jats:italic>\n                      <jats:sup>-\/-<\/jats:sup>\n                      background. We show that human\n                      <jats:italic>SMN2<\/jats:italic>\n                      is spliced in zebrafish as it is in humans and makes low levels of SMN protein. Moreover, we show that an antisense oligonucleotide that enhances correct\n                      <jats:italic>hSMN2<\/jats:italic>\n                      splicing increases full-length\n                      <jats:italic>hSMN<\/jats:italic>\n                      RNA in this model. When we placed this transgene on the\n                      <jats:italic>smn<\/jats:italic>\n                      mutant background it rescued the neuromuscular presynaptic SV2 defect that occurs in\n                      <jats:italic>smn<\/jats:italic>\n                      mutants and increased their survival.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      We have generated a transgenic fish carrying the human\n                      <jats:italic>hSMN2<\/jats:italic>\n                      gene. This gene is spliced in fish as it is in humans and mice suggesting a conserved splicing mechanism in these vertebrates. Moreover, antisense targeting of an intronic splicing silencer site increased the amount of full length SMN generated from this transgene. Having this transgene on the\n                      <jats:italic>smn<\/jats:italic>\n                      mutant fish rescued the presynaptic defect and increased survival. This model of zebrafish SMA has all of the components of human SMA and can thus be used to understand motoneuron dysfunction in SMA, can be used as an vivo test for drugs or antisense approaches that increase full-length SMN, and can be developed for drug screening.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/1750-1326-6-24","type":"journal-article","created":{"date-parts":[[2011,4,2]],"date-time":"2011-04-02T16:03:36Z","timestamp":1301760216000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Generation and Characterization of a genetic zebrafish model of SMA carrying the human SMN2gene"],"prefix":"10.1186","volume":"6","author":[{"given":"Le T","family":"Hao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur HM","family":"Burghes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine E","family":"Beattie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2011,3,28]]},"reference":[{"key":"180_CR1","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, Burglen L, Reboullet S, Clermont O, Burlet P, Viollet L, Benichou B, Cruaud C, Millasseau P, Zeviani M, et al: Identification and characterization of a spinal muscular atrophy-determining gene. 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