{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T10:21:26Z","timestamp":1789986086736,"version":"4.0.1"},"reference-count":76,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,1,25]],"date-time":"2017-01-25T00:00:00Z","timestamp":1485302400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000894","name":"Spinal Muscular Atrophy Foundation","doi-asserted-by":"publisher","award":["C59935"],"award-info":[{"award-number":["C59935"]}],"id":[{"id":"10.13039\/100000894","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN217643"],"award-info":[{"award-number":["RGPIN217643"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p><jats:italic>Smn<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> transgenic mouse is a model of the mildest form of spinal muscular atrophy.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Although there is a loss of spinal motoneurons in 11\u2010month\u2010old animals, muscular force is maintained.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>This maintained muscular force is mediated by reinnervation of the denervated fibres by surviving motoneurons.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The spinal motoneurons in these animals do not show an increased susceptibility to death after nerve injury and they retain their regenerative capacity.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We conclude that the hypothesized immaturity of the neuromuscular system in this model cannot explain the loss of motoneurons by systematic die\u2010back.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Spinal muscular atrophy (SMA) is a common autosomal recessive disorder in humans and is the leading genetic cause of infantile death. Patients lack the <jats:italic>SMN1<\/jats:italic> gene with the severity of the disease depending on the number of copies of the highly homologous <jats:italic>SMN2<\/jats:italic> gene. Although motoneuron death in the <jats:italic>Smn<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> transgenic mouse model of the mildest form of SMA, SMA type III, has been reported, we have used retrograde tracing of sciatic and femoral motoneurons in the hindlimb with recording of muscle and motor unit isometric forces to count the number of motoneurons with intact neuromuscular connections. Thereby, we investigated whether incomplete maturation of the neuromuscular system induced by survival motoneuron protein (SMN) defects is responsible for die\u2010back of axons relative to survival of motoneurons. First, a reduction of \u223c30% of backlabelled motoneurons began relatively late, at 11\u00a0months of age, with a significant loss of 19% at 7\u00a0months. Motor axon die\u2010back was affirmed by motor unit number estimation. Loss of functional motor units was fully compensated by axonal sprouting to retain normal contractile force in four hindlimb muscles (three fast\u2010twitch and one slow\u2010twitch) innervated by branches of the sciatic nerve. Second, our evaluation of whether axotomy of motoneurons in the adult <jats:italic>Smn<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup> transgenic mouse increases their susceptibility to cell death demonstrated that all the motoneurons survived and they sustained their capacity to regenerate their nerve fibres. It is concluded the systematic die\u2010back of motoneurons that innervate both fast\u2010 and slow\u2010twitch muscle fibres is not related to immaturity of the neuromuscular system in SMA.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp273404","type":"journal-article","created":{"date-parts":[[2016,11,28]],"date-time":"2016-11-28T07:52:52Z","timestamp":1480319572000},"page":"1815-1829","source":"Crossref","is-referenced-by-count":13,"title":["Compensatory axon sprouting for very slow axonal die\u2010back in a transgenic model of spinal muscular atrophy type III"],"prefix":"10.1113","volume":"595","author":[{"given":"Esther","family":"Udina","sequence":"first","affiliation":[{"name":"Neuroscience and Mental Health Institute, Faculty of Medicine and Dentistry University of Alberta  Edmonton AB Canada T6G 2S2"},{"name":"Institute of Neurosciences and Department of Cell Biology, Physiology and Immunology Universitat Aut\u00f2noma de Barcelona, and Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas (CIBERNED)  Bellaterra Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles T.","family":"Putman","sequence":"additional","affiliation":[{"name":"Neuroscience and Mental Health Institute, Faculty of Medicine and Dentistry University of Alberta  Edmonton AB Canada T6G 2S2"},{"name":"Exercise Biochemistry Laboratory, Faculty of Physical Education and Recreation University of Alberta  Edmonton AB Canada T6G 2H9"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6771-1200","authenticated-orcid":false,"given":"Luke R.","family":"Harris","sequence":"additional","affiliation":[{"name":"Neuroscience and Mental Health Institute, Faculty of Medicine and Dentistry University of Alberta  Edmonton AB Canada T6G 2S2"},{"name":"Exercise Biochemistry Laboratory, Faculty of Physical Education and Recreation University of Alberta  Edmonton AB Canada T6G 2H9"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Tyreman","sequence":"additional","affiliation":[{"name":"Neuroscience and Mental Health Institute, Faculty of Medicine and Dentistry University of Alberta  Edmonton AB Canada T6G 2S2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria E.","family":"Cook","sequence":"additional","affiliation":[{"name":"Neuroscience and Mental Health Institute, Faculty of Medicine and Dentistry University of Alberta  Edmonton AB Canada T6G 2S2"},{"name":"Exercise Biochemistry Laboratory, Faculty of Physical Education and Recreation University of Alberta  Edmonton AB Canada T6G 2H9"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tessa","family":"Gordon","sequence":"additional","affiliation":[{"name":"Neuroscience and Mental Health Institute, Faculty of Medicine and Dentistry University of Alberta  Edmonton AB Canada T6G 2S2"},{"name":"Division of Rehabilitation and Physical Medicine of the Faculty of Medicine and Dentistry University of Alberta  Edmonton AB Canada T6G 2S2"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,1,25]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"37","article-title":"Quantitative histology of Wallerian degeneration: I. 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