{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T04:33:10Z","timestamp":1788323590862,"version":"build-2803163510"},"reference-count":59,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T00:00:00Z","timestamp":1659312000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["NS116400"],"award-info":[{"award-number":["NS116400"]}]},{"name":"National Science Foundation \/ Graduate Research Fellowship Program"},{"name":"NIH","award":["NS102451"],"award-info":[{"award-number":["NS102451"]}]},{"name":"NIH","award":["NS114218"],"award-info":[{"award-number":["NS114218"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\n                    Spinal muscular atrophy (SMA) is a neurodegenerative disease characterized by loss of motor neurons and skeletal muscle atrophy which is caused by ubiquitous deficiency in the survival motor neuron (SMN) protein. Several cellular defects contribute to sensory-motor circuit pathology in SMA mice, but the underlying mechanisms have often been studied in one mouse model without validation in other available models. Here, we used\n                    <jats:italic>Smn<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>2B\/-<\/jats:italic>\n                    <\/jats:sup>\n                    mice to investigate specific behavioral, morphological, and functional aspects of SMA pathology that we previously characterized in the\n                    <jats:italic>SMN\u03947<\/jats:italic>\n                    model.\n                    <jats:italic>Smn<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>2B\/-<\/jats:italic>\n                    <\/jats:sup>\n                    SMA mice on a pure FVB\/N background display deficits in body weight gain and muscle strength with onset in the second postnatal week and median survival of 19 days. Morphological analysis revealed severe loss of proprioceptive synapses on the soma of motor neurons and prominent denervation of neuromuscular junctions (NMJs) in axial but not distal muscles. In contrast, no evidence of cell death emerged from analysis of several distinct pools of lumbar motor neurons known to be lost in the disease. Moreover, SMA motor neurons from\n                    <jats:italic>Smn<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>2B\/-<\/jats:italic>\n                    <\/jats:sup>\n                    mice showed robust nuclear accumulation of p53 but lack of phosphorylation of serine 18 at its amino-terminal, which selectively marks degenerating motor neurons in the\n                    <jats:italic>SMN\u03947<\/jats:italic>\n                    mouse model. These results indicate that NMJ denervation and deafferentation, but not motor neuron death, are conserved features of SMA pathology in\n                    <jats:italic>Smn<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>2B\/-<\/jats:italic>\n                    <\/jats:sup>\n                    mice.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0267990","type":"journal-article","created":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T14:57:03Z","timestamp":1659365823000},"page":"e0267990","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":15,"title":["Neuromuscular denervation and deafferentation but not motor neuron death are disease features in the Smn2B\/- mouse model of SMA"],"prefix":"10.1371","volume":"17","author":[{"given":"Maria J.","family":"Carlini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina K.","family":"Triplett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9168-5628","authenticated-orcid":true,"given":"Livio","family":"Pellizzoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,8,1]]},"reference":[{"key":"pone.0267990.ref001","doi-asserted-by":"crossref","first-page":"8691","DOI":"10.1523\/JNEUROSCI.0417-15.2015","article-title":"Disease Mechanisms and Therapeutic Approaches in Spinal Muscular Atrophy","volume":"35","author":"S Tisdale","year":"2015","journal-title":"J Neurosci"},{"key":"pone.0267990.ref002","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1146\/annurev-genom-102319-103602","article-title":"Twenty-Five Years of Spinal Muscular Atrophy Research: From Phenotype to Genotype to Therapy, and What Comes Next","volume":"21","author":"B Wirth","year":"2020","journal-title":"Annu Rev Genomics Hum Genet"},{"key":"pone.0267990.ref003","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/0092-8674(95)90460-3","article-title":"Identification and characterization of a spinal muscular atrophy- determining gene","volume":"80","author":"S Lefebvre","year":"1995","journal-title":"Cell"},{"key":"pone.0267990.ref004","doi-asserted-by":"crossref","first-page":"6307","DOI":"10.1073\/pnas.96.11.6307","article-title":"A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy","volume":"96","author":"CL Lorson","year":"1999","journal-title":"Proc Natl Acad Sci USA"},{"key":"pone.0267990.ref005","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/nature10485","article-title":"Peripheral SMN restoration is essential for long-term rescue of a severe spinal muscular atrophy mouse model","volume":"478","author":"Y Hua","year":"2011","journal-title":"Nature"},{"key":"pone.0267990.ref006","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1126\/science.1250127","article-title":"Motor neuron disease. 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