{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T22:04:24Z","timestamp":1790978664806,"version":"4.1.0"},"reference-count":58,"publisher":"Elsevier BV","issue":"33","license":[{"start":{"date-parts":[[2012,8,1]],"date-time":"2012-08-01T00:00:00Z","timestamp":1343779200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,10,9]],"date-time":"2020-10-09T00:00:00Z","timestamp":1602201600000},"content-version":"vor","delay-in-days":2991,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Biological Chemistry"],"published-print":{"date-parts":[[2012,8]]},"DOI":"10.1074\/jbc.m112.359000","type":"journal-article","created":{"date-parts":[[2012,6,21]],"date-time":"2012-06-21T13:29:47Z","timestamp":1340285387000},"page":"27335-27344","source":"Crossref","is-referenced-by-count":158,"title":["Targeted Depletion of TDP-43 Expression in the Spinal Cord Motor Neurons Leads to the Development of Amyotrophic Lateral Sclerosis-like Phenotypes in Mice"],"prefix":"10.1016","volume":"287","author":[{"given":"Lien-Szu","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Cheng","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.-K. James","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1074\/jbc.M112.359000_bib1","first-page":"15","article-title":"Clinical limits of amyotrophic lateral sclerosis","volume":"36","author":"Mulder","year":"1982","journal-title":"Adv. Neurol."},{"key":"10.1074\/jbc.M112.359000_bib2","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1038\/nrn1971","article-title":"Molecular biology of amyotrophic lateral sclerosis. Insights from genetics","volume":"7","author":"Pasinelli","year":"2006","journal-title":"Nat. Rev. Neurosci."},{"key":"10.1074\/jbc.M112.359000_bib3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1750-1172-4-3","article-title":"Amyotrophic lateral sclerosis","volume":"4","author":"Wijesekera","year":"2009","journal-title":"Orphanet J. Rare Dis."},{"key":"10.1074\/jbc.M112.359000_bib4","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.1007\/s00415-006-0195-y","article-title":"Amyotrophic lateral sclerosis in an urban setting. A population based study of inner city London","volume":"253","author":"Johnston","year":"2006","journal-title":"J. Neurol."},{"key":"10.1074\/jbc.M112.359000_bib5","doi-asserted-by":"crossref","first-page":"439","DOI":"10.3109\/17482961003610853","article-title":"The sex ratio in amyotrophic lateral sclerosis. A population based study","volume":"11","author":"Manjaly","year":"2010","journal-title":"Amyotroph. Lateral Scler."},{"key":"10.1074\/jbc.M112.359000_bib6","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1136\/jnnp.2004.048652","article-title":"Molecular and cellular pathways of neurodegeneration in motor neurone disease","volume":"76","author":"Shaw","year":"2005","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"10.1074\/jbc.M112.359000_bib7","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1126\/science.1154584","article-title":"TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis","volume":"319","author":"Sreedharan","year":"2008","journal-title":"Science"},{"key":"10.1074\/jbc.M112.359000_bib8","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1016\/j.cell.2009.03.006","article-title":"Rethinking ALS. The FUS about TDP-43","volume":"136","author":"Lagier-Tourenne","year":"2009","journal-title":"Cell"},{"key":"10.1074\/jbc.M112.359000_bib9","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1016\/S1474-4422(10)70195-2","article-title":"TDP-43 and FUS in amyotrophic lateral sclerosis and frontotemporal dementia","volume":"9","author":"Mackenzie","year":"2010","journal-title":"Lancet Neurol."},{"key":"10.1074\/jbc.M112.359000_bib10","doi-asserted-by":"crossref","first-page":"3584","DOI":"10.1128\/jvi.69.6.3584-3596.1995","article-title":"Cloning and characterization of a novel cellular protein, TDP-43, that binds to human immunodeficiency virus type 1 TAR DNA sequence motifs","volume":"69","author":"Ou","year":"1995","journal-title":"J. Virol."},{"key":"10.1074\/jbc.M112.359000_bib11","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/S0888-7543(03)00214-3","article-title":"Structural diversity and functional implications of the eukaryotic TDP gene family","volume":"83","author":"Wang","year":"2004","journal-title":"Genomics"},{"key":"10.1074\/jbc.M112.359000_bib12","doi-asserted-by":"crossref","first-page":"867","DOI":"10.2741\/2727","article-title":"Multiple roles of TDP-43 in gene expression, splicing regulation, and human disease","volume":"13","author":"Buratti","year":"2008","journal-title":"Front. Biosci."},{"key":"10.1074\/jbc.M112.359000_bib13","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1111\/j.1471-4159.2007.05190.x","article-title":"TDP-43, the signature protein of FTLD-U, is a neuronal activity-responsive factor","volume":"105","author":"Wang","year":"2008","journal-title":"J. Neurochem."},{"key":"10.1074\/jbc.M112.359000_bib14","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1016\/j.bbrc.2006.10.093","article-title":"TDP-43 is a component of ubiquitin-positive Tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis","volume":"351","author":"Arai","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1074\/jbc.M112.359000_bib15","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1126\/science.1134108","article-title":"Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis","volume":"314","author":"Neumann","year":"2006","journal-title":"Science"},{"key":"10.1074\/jbc.M112.359000_bib16","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1016\/j.conb.2007.08.005","article-title":"TDP-43, a novel neurodegenerative proteinopathy","volume":"17","author":"Forman","year":"2007","journal-title":"Curr. Opin. Neurobiol."},{"key":"10.1074\/jbc.M112.359000_bib17","doi-asserted-by":"crossref","first-page":"232","DOI":"10.3390\/ijms10010232","article-title":"Molecular neuropathology of TDP-43 proteinopathies","volume":"10","author":"Neumann","year":"2009","journal-title":"Int. J. Mol. Sci."},{"key":"10.1074\/jbc.M112.359000_bib18","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1001\/archneur.64.10.1388","article-title":"TDP-43 proteinopathy in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Protein misfolding diseases without amyloidosis","volume":"64","author":"Neumann","year":"2007","journal-title":"Arch. Neurol."},{"key":"10.1074\/jbc.M112.359000_bib19","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s00401-007-0308-4","article-title":"Amyotrophic lateral sclerosis models and human neuropathology. Similarities and differences","volume":"115","author":"Kato","year":"2008","journal-title":"Acta Neuropathol."},{"key":"10.1074\/jbc.M112.359000_bib20","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.pneurobio.2008.01.001","article-title":"Transgenics, toxicity and therapeutics in rodent models of mutant SOD1-mediated familial ALS","volume":"85","author":"Turner","year":"2008","journal-title":"Prog. Neurobiol."},{"key":"10.1074\/jbc.M112.359000_bib21","doi-asserted-by":"crossref","first-page":"1772","DOI":"10.1126\/science.8209258","article-title":"Motor neuron degeneration in mice that express a human Cu,Zn-superoxide dismutase mutation","volume":"264","author":"Gurney","year":"1994","journal-title":"Science"},{"key":"10.1074\/jbc.M112.359000_bib22","first-page":"51","article-title":"Pathogenic mechanisms in familial amyotrophic lateral sclerosis due to mutation of Cu,Zn-superoxide dismutase","volume":"44","author":"Gurney","year":"1996","journal-title":"Pathol. Biol."},{"key":"10.1074\/jbc.M112.359000_bib23","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/s00401-005-1019-3","article-title":"Redox system expression in the motor neurons in amyotrophic lateral sclerosis (ALS). Immunohistochemical studies on sporadic ALS, superoxide dismutase 1 (SOD1)-mutated familial ALS, and SOD1-mutated ALS animal models","volume":"110","author":"Kato","year":"2005","journal-title":"Acta Neuropathol."},{"key":"10.1074\/jbc.M112.359000_bib24","doi-asserted-by":"crossref","first-page":"18809","DOI":"10.1073\/pnas.0908767106","article-title":"TDP-43 mutant transgenic mice develop features of ALS and frontotemporal lobar degeneration","volume":"106","author":"Wegorzewska","year":"2009","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"10.1074\/jbc.M112.359000_bib25","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1084\/jem.20092164","article-title":"Elevated expression of TDP-43 in the forebrain of mice is sufficient to cause neurological and pathological phenotypes mimicking FTLD-U","volume":"207","author":"Tsai","year":"2010","journal-title":"J. Exp. Med."},{"key":"10.1074\/jbc.M112.359000_bib26","doi-asserted-by":"crossref","first-page":"3858","DOI":"10.1073\/pnas.0912417107","article-title":"TDP-43 transgenic mice develop spastic paralysis and neuronal inclusions characteristic of ALS and frontotemporal lobar degeneration","volume":"107","author":"Wils","year":"2010","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"10.1074\/jbc.M112.359000_bib27","doi-asserted-by":"crossref","first-page":"e1000887","DOI":"10.1371\/journal.pgen.1000887","article-title":"Transgenic rat model of neurodegeneration caused by mutation in the TDP gene","volume":"6","author":"Zhou","year":"2010","journal-title":"PLoS Genet."},{"key":"10.1074\/jbc.M112.359000_bib28","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1172\/JCI44867","article-title":"Dysregulation of the ALS-associated gene TDP-43 leads to neuronal death and degeneration in mice","volume":"121","author":"Igaz","year":"2011","journal-title":"J. Clin. Invest."},{"key":"10.1074\/jbc.M112.359000_bib29","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/j.molmed.2008.09.001","article-title":"TDP-43. An emerging new player in neurodegenerative diseases","volume":"14","author":"Wang","year":"2008","journal-title":"Trends Mol. Med."},{"key":"10.1074\/jbc.M112.359000_bib30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0065-2660(09)66001-6","article-title":"The molecular links between TDP-43 dysfunction and neurodegeneration","volume":"66","author":"Buratti","year":"2009","journal-title":"Adv. Genet."},{"key":"10.1074\/jbc.M112.359000_bib31","first-page":"211","volume":"6","author":"Chen-Plotkin","year":"2010","journal-title":"Nat. Rev."},{"key":"10.1074\/jbc.M112.359000_bib32","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1002\/dvg.20584","article-title":"TDP-43, a neuropathosignature factor, is essential for early mouse embryogenesis","volume":"48","author":"Wu","year":"2010","journal-title":"Genesis"},{"key":"10.1074\/jbc.M112.359000_bib33","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/S0896-6273(01)00287-2","article-title":"Patterning of muscle acetylcholine receptor gene expression in the absence of motor innervation","volume":"30","author":"Yang","year":"2001","journal-title":"Neuron"},{"key":"10.1074\/jbc.M112.359000_bib34","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/S0896-6273(01)80026-X","article-title":"Requirement for the homeobox gene Hb9 in the consolidation of motor neuron identity","volume":"23","author":"Arber","year":"1999","journal-title":"Neuron"},{"key":"10.1074\/jbc.M112.359000_bib35","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.neuron.2006.02.020","article-title":"Cooperation between GDNF\/Ret and ephrinA\/EphA4 signals for motor-axon pathway selection in the limb","volume":"50","author":"Kramer","year":"2006","journal-title":"Neuron"},{"key":"10.1074\/jbc.M112.359000_bib36","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1002\/cne.21163","article-title":"Localization of TrkC to Schwann cells and effects of neurotrophin-3 signaling at neuromuscular synapses","volume":"501","author":"Hess","year":"2007","journal-title":"J. Comp. Neurol."},{"key":"10.1074\/jbc.M112.359000_bib37","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1038\/nn2053","article-title":"Retrograde regulation of motoneuron differentiation by muscle \u03b2-catenin","volume":"11","author":"Li","year":"2008","journal-title":"Nat. Neurosci."},{"key":"10.1074\/jbc.M112.359000_bib38","doi-asserted-by":"crossref","first-page":"e17768","DOI":"10.1371\/journal.pone.0017768","article-title":"Axonal regeneration and neuronal function are preserved in motor neurons lacking \u03b2-actin in vivo","volume":"6","author":"Cheever","year":"2011","journal-title":"PLoS One"},{"key":"10.1074\/jbc.M112.359000_bib39","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/1749-8104-2-13","article-title":"Lateral motor column axons execute a ternary trajectory choice between limb and body tissues","volume":"2","author":"Luria","year":"2007","journal-title":"Neural. Dev."},{"key":"10.1074\/jbc.M112.359000_bib40","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1080\/17482960701538759","article-title":"A method comparison in monitoring disease progression of G93A mouse model of ALS","volume":"8","author":"Zhou","year":"2007","journal-title":"Amyotroph. Lateral Scler."},{"key":"10.1074\/jbc.M112.359000_bib41","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/0022-510X(95)00058-A","article-title":"Thoracic radicular symptoms in amyotrophic lateral sclerosis","volume":"129","author":"Newman","year":"1995","journal-title":"J. Neurol. Sci."},{"key":"10.1074\/jbc.M112.359000_bib42","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1002\/(SICI)1097-4598(199701)20:1<45::AID-MUS6>3.0.CO;2-H","article-title":"Progressive motor neuron impairment in an animal model of familial amyotrophic lateral sclerosis","volume":"20","author":"Azzouz","year":"1997","journal-title":"Muscle Nerve"},{"key":"10.1074\/jbc.M112.359000_bib43","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1152\/jn.1977.40.3.667","article-title":"Anatomy of medial gastrocnemius and soleus motor nuclei in cat spinal cord","volume":"40","author":"Burke","year":"1977","journal-title":"J. Neurophysiol"},{"key":"10.1074\/jbc.M112.359000_bib44","doi-asserted-by":"crossref","first-page":"13588","DOI":"10.1073\/pnas.0906809106","article-title":"\u03b3 and \u03b1 motor neurons distinguished by expression of transcription factor Err3","volume":"106","author":"Friese","year":"2009","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"10.1074\/jbc.M112.359000_bib45","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/1749-8104-4-42","article-title":"\u03b3 Motor neurons express distinct genetic markers at birth and require muscle spindle-derived GDNF for postnatal survival","volume":"4","author":"Shneider","year":"2009","journal-title":"Neural. Dev."},{"key":"10.1074\/jbc.M112.359000_bib46","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/0361-9230(93)90265-D","article-title":"Clinicopathological features of primary lateral sclerosis are different from amyotrophic lateral sclerosis","volume":"30","author":"Hudson","year":"1993","journal-title":"Brain Res. Bull."},{"key":"10.1074\/jbc.M112.359000_bib47","doi-asserted-by":"crossref","first-page":"e20371","DOI":"10.1371\/journal.pone.0020371","article-title":"Neuronal function and dysfunction of Drosophila dTDP","volume":"6","author":"Lin","year":"2011","journal-title":"PLoS One"},{"key":"10.1074\/jbc.M112.359000_bib48","doi-asserted-by":"crossref","first-page":"12306","DOI":"10.1073\/pnas.97.22.12306","article-title":"Reduction of axonal caliber does not alleviate motor neuron disease caused by mutant superoxide dismutase 1","volume":"97","author":"Nguyen","year":"2000","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"10.1074\/jbc.M112.359000_bib49","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1002\/(SICI)1098-1136(199807)23:3<249::AID-GLIA7>3.0.CO;2-#","article-title":"Relationship of microglial and astrocytic activation to disease onset and progression in a transgenic model of familial ALS","volume":"23","author":"Hall","year":"1998","journal-title":"Glia"},{"key":"10.1074\/jbc.M112.359000_bib50","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1038\/nrm1742","article-title":"Opinion. What is the role of protein aggregation in neurodegeneration?","volume":"6","author":"Ross","year":"2005","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1074\/jbc.M112.359000_bib51","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1016\/j.febslet.2009.04.019","article-title":"Depletion of TDP-43 affects Drosophila motoneurons terminal synapsis and locomotive behavior","volume":"583","author":"Feiguin","year":"2009","journal-title":"FEBS Lett."},{"key":"10.1074\/jbc.M112.359000_bib52","doi-asserted-by":"crossref","first-page":"e15878","DOI":"10.1371\/journal.pone.0015878","article-title":"The C-terminal TDP-43 fragments have a high aggregation propensity and harm neurons by a dominant-negative mechanism","volume":"5","author":"Yang","year":"2010","journal-title":"PLoS One"},{"key":"10.1074\/jbc.M112.359000_bib53","doi-asserted-by":"crossref","first-page":"16325","DOI":"10.1073\/pnas.1003459107","article-title":"Altered distributions of Gemini of coiled bodies and mitochondria in motor neurons of TDP-43 transgenic mice","volume":"107","author":"Shan","year":"2010","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"10.1074\/jbc.M112.359000_bib54","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.nbd.2010.06.017","article-title":"Progressive motor weakness in transgenic mice expressing human TDP-43","volume":"40","author":"Stallings","year":"2010","journal-title":"Neurobiol. Dis."},{"key":"10.1074\/jbc.M112.359000_bib55","doi-asserted-by":"crossref","first-page":"10851","DOI":"10.1523\/JNEUROSCI.1630-10.2010","article-title":"Wild-type human TDP-43 expression causes TDP-43 phosphorylation, mitochondrial aggregation, motor deficits, and early mortality in transgenic mice","volume":"30","author":"Xu","year":"2010","journal-title":"J. Neurosci."},{"key":"10.1074\/jbc.M112.359000_bib56","doi-asserted-by":"crossref","first-page":"44441","DOI":"10.1074\/jbc.M111.237115","article-title":"Regulation of autophagy by neuropathological protein TDP-43","volume":"286","author":"Bose","year":"2011","journal-title":"J. Biol. Chem."},{"key":"10.1074\/jbc.M112.359000_bib57","doi-asserted-by":"crossref","first-page":"18845","DOI":"10.1074\/jbc.M111.231118","article-title":"A \u201dtwo-hit\u201c hypothesis for inclusion formation by carboxyl-terminal fragments of TDP-43 protein linked to RNA depletion and impaired microtubule-dependent transport","volume":"286","author":"Pesiridis","year":"2011","journal-title":"J. Biol. Chem."},{"key":"10.1074\/jbc.M112.359000_bib58","doi-asserted-by":"crossref","first-page":"18664","DOI":"10.1074\/jbc.M111.231209","article-title":"A seeding reaction recapitulates intracellular formation of Sarkosyl-insoluble transactivation response element (TAR) DNA-binding protein-43 inclusions","volume":"286","author":"Furukawa","year":"2011","journal-title":"J. Biol. Chem."}],"container-title":["Journal of Biological Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0021925820477531?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0021925820477531?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1074\/jbc.M112.359000","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,25]],"date-time":"2024-04-25T23:38:11Z","timestamp":1714088291000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0021925820477531"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,8]]},"references-count":58,"journal-issue":{"issue":"33","published-print":{"date-parts":[[2012,8]]}},"alternative-id":["S0021925820477531"],"URL":"https:\/\/doi.org\/10.1074\/jbc.m112.359000","relation":{},"ISSN":["0021-9258"],"issn-type":[{"value":"0021-9258","type":"print"}],"subject":[],"published":{"date-parts":[[2012,8]]}}}