{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T22:04:42Z","timestamp":1791842682667,"version":"4.3.4"},"reference-count":25,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5875","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2008,4,25]]},"abstract":"<jats:p>\n                    Homozygous deletion of the survival motor neuron 1 gene (\n                    <jats:italic>SMN1<\/jats:italic>\n                    ) causes spinal muscular atrophy (SMA), the most frequent genetic cause of early childhood lethality. In rare instances, however, individuals are asymptomatic despite carrying the same\n                    <jats:italic>SMN1<\/jats:italic>\n                    mutations as their affected siblings, thereby suggesting the influence of modifier genes. We discovered that unaffected\n                    <jats:italic>SMN1<\/jats:italic>\n                    -deleted females exhibit significantly higher expression of plastin 3 (\n                    <jats:italic>PLS3<\/jats:italic>\n                    ) than their SMA-affected counterparts. We demonstrated that PLS3 is important for axonogenesis through increasing the F-actin level. Overexpression of PLS3 rescued the axon length and outgrowth defects associated with SMN down-regulation in motor neurons of SMA mouse embryos and in zebrafish. Our study suggests that defects in axonogenesis are the major cause of SMA, thereby opening new therapeutic options for SMA and similar neuromuscular diseases.\n                  <\/jats:p>","DOI":"10.1126\/science.1155085","type":"journal-article","created":{"date-parts":[[2008,4,25]],"date-time":"2008-04-25T13:16:06Z","timestamp":1209129366000},"page":"524-527","source":"Crossref","is-referenced-by-count":459,"title":["Plastin 3 Is a Protective Modifier of Autosomal Recessive Spinal Muscular Atrophy"],"prefix":"10.1126","volume":"320","author":[{"given":"Gabriela E.","family":"Oprea","sequence":"first","affiliation":[{"name":"Institute of Human Genetics, University of Cologne, 50931 Cologne, Germany."},{"name":"Institute of Genetics, University of Cologne, 50931 Cologne, Germany."},{"name":"Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany."},{"name":"Centre for Molecular Neurobiology and Department of Neuroscience, The Ohio State University, Columbus, OH 43210, USA."},{"name":"Emory University School of Medicine, Department of Cell Biology, Atlanta, GA 30322, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Kro\u0308ber","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University of Cologne, 50931 Cologne, Germany."},{"name":"Institute of Genetics, University of Cologne, 50931 Cologne, Germany."},{"name":"Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany."},{"name":"Centre for Molecular Neurobiology and Department of Neuroscience, The Ohio State University, Columbus, OH 43210, USA."},{"name":"Emory University School of Medicine, Department of Cell Biology, Atlanta, GA 30322, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle L.","family":"McWhorter","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University of Cologne, 50931 Cologne, Germany."},{"name":"Institute of Genetics, University of Cologne, 50931 Cologne, Germany."},{"name":"Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany."},{"name":"Centre for Molecular Neurobiology and Department of Neuroscience, The Ohio State University, Columbus, OH 43210, USA."},{"name":"Emory University School of Medicine, Department of Cell Biology, Atlanta, GA 30322, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilfried","family":"Rossoll","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University of Cologne, 50931 Cologne, Germany."},{"name":"Institute of Genetics, University of Cologne, 50931 Cologne, Germany."},{"name":"Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany."},{"name":"Centre for Molecular Neurobiology and Department of Neuroscience, The Ohio State University, Columbus, OH 43210, USA."},{"name":"Emory University School of Medicine, Department of Cell Biology, Atlanta, GA 30322, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Mu\u0308ller","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University of Cologne, 50931 Cologne, Germany."},{"name":"Institute of Genetics, University of Cologne, 50931 Cologne, Germany."},{"name":"Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany."},{"name":"Centre for Molecular Neurobiology and Department of Neuroscience, The Ohio State University, Columbus, OH 43210, USA."},{"name":"Emory University School of Medicine, Department of Cell Biology, Atlanta, GA 30322, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Krawczak","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University of Cologne, 50931 Cologne, Germany."},{"name":"Institute of Genetics, University of Cologne, 50931 Cologne, Germany."},{"name":"Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany."},{"name":"Centre for Molecular Neurobiology and Department of Neuroscience, The Ohio State University, Columbus, OH 43210, USA."},{"name":"Emory University School of Medicine, Department of Cell Biology, Atlanta, GA 30322, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary J.","family":"Bassell","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University of Cologne, 50931 Cologne, Germany."},{"name":"Institute of Genetics, University of Cologne, 50931 Cologne, Germany."},{"name":"Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany."},{"name":"Centre for Molecular Neurobiology and Department of Neuroscience, The Ohio State University, Columbus, OH 43210, USA."},{"name":"Emory University School of Medicine, Department of Cell Biology, Atlanta, GA 30322, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine E.","family":"Beattie","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University of Cologne, 50931 Cologne, Germany."},{"name":"Institute of Genetics, University of Cologne, 50931 Cologne, Germany."},{"name":"Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany."},{"name":"Centre for Molecular Neurobiology and Department of Neuroscience, The Ohio State University, Columbus, OH 43210, USA."},{"name":"Emory University School of Medicine, Department of Cell Biology, Atlanta, GA 30322, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brunhilde","family":"Wirth","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University of Cologne, 50931 Cologne, Germany."},{"name":"Institute of Genetics, University of Cologne, 50931 Cologne, Germany."},{"name":"Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany."},{"name":"Centre for Molecular Neurobiology and Department of Neuroscience, The Ohio State University, Columbus, OH 43210, USA."},{"name":"Emory University School of Medicine, Department of Cell Biology, Atlanta, GA 30322, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/0092-8674(95)90460-3","volume":"80","year":"1995","unstructured":"S. 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Gertler, Neuron40, 209 (2003).","journal-title":"Neuron"},{"key":"e_1_3_1_24_2","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1093\/hmg\/9.3.333","volume":"9","year":"2000","unstructured":"U. R. Monaniet al., Hum. Mol. Genet.9, 333 (2000).","journal-title":"Hum. Mol. Genet."},{"key":"e_1_3_1_25_2","doi-asserted-by":"crossref","first-page":"11014","DOI":"10.1523\/JNEUROSCI.1637-06.2006","volume":"26","year":"2006","unstructured":"T. L. Carrelet al., J. Neurosci.26, 11014 (2006).","journal-title":"J. Neurosci."},{"key":"e_1_3_1_26_2","unstructured":"We thank SMA families and genetic counselors especially S. Rudnik-Sch\u00f6neborn and K. Zerres; J. L. Schultze S. Debey P. N\u00fcrnberg M. Reza-Toliat F. Rivero-Crespo and F.G. Hanisch at the Univ. of Cologne for allowing us to use their facilities and for helpful advice; G. Morris (Oswestry UK) for the mouse anti-survival motor neurons proteins 1 antibody; and B. Wollnik C. Kubisch and R. Heller for critical reading of the manuscript. This work was supported by the Center for Molecular Medicine Cologne and the Deutsche Forschungsgemeinschaft (B.W.) families of SMA (W.R. and M.L.M.) and NIH grants RO1NS50414 (C.E.B.) and HD055835 (G.J.B.)."}],"updated-by":[{"DOI":"10.1126\/science.adq4773","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2024,5,30]],"date-time":"2024-05-30T00:00:00Z","timestamp":1717027200000}}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1155085","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T03:36:03Z","timestamp":1704857763000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1155085"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,4,25]]},"references-count":25,"journal-issue":{"issue":"5875","published-print":{"date-parts":[[2008,4,25]]}},"alternative-id":["10.1126\/science.1155085"],"URL":"https:\/\/doi.org\/10.1126\/science.1155085","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1108363.565197","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1108363.564402","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1108363.564829","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1108363.565533","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1108363.620219","asserted-by":"object"}]},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,4,25]]}}}