{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T04:52:58Z","timestamp":1791089578440,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,6,26]],"date-time":"2006-06-26T00:00:00Z","timestamp":1151280000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2006,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Homozygous mutation in the <jats:italic>ALS2<\/jats:italic> gene and the resulting loss of the guanine exchange factor activity of the ALS2 protein is causative for autosomal recessive early\u2010onset motor neuron disease that is thought to predominantly affect upper motor neurons. The goal of this study was to elucidate how the motor system is affected by the deletion of ALS2.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>ALS2\u2010deficient mice were generated by gene targeting. Motor function and upper and lower motor neuron pathology were examined in ALS2\u2010deficient mice and in mutant superoxide dismutase 1 (SOD1) mice that develop ALS\u2010like disease from expression of an ALS\u2010linked mutation in SOD1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>ALS2\u2010deficient mice demonstrated progressive axonal degeneration in the lateral spinal cord that is also prominent in mutant SOD1 mice. Despite the vulnerability of these spinal axons, lower motor neurons in ALS2\u2010deficient mice were preserved. Behavioral studies demonstrated slowed movement without muscle weakness in <jats:italic>ALS2<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice, consistent with upper motor neuron defects that lead to spasticity in humans.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>The combined evidence from mice and humans shows that deficiency in ALS2 causes an upper motor neuron disease that in humans closely resembles a severe form of hereditary spastic paralysis, and that is quite distinct from amyotrophic lateral sclerosis. Ann Neurol 2006;60:95\u2013104<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.20888","type":"journal-article","created":{"date-parts":[[2006,6,26]],"date-time":"2006-06-26T16:05:23Z","timestamp":1151337923000},"page":"95-104","source":"Crossref","is-referenced-by-count":67,"title":["Progressive spinal axonal degeneration and slowness in ALS2\u2010deficient mice"],"prefix":"10.1002","volume":"60","author":[{"given":"Koji","family":"Yamanaka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy M.","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"McAlonis\u2010Downes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Joo","family":"Chun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Don W.","family":"Cleveland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,6,26]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/35097565"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.27.070203.144244"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0794-425"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s100480050049"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1998.5637"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1001-166"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1001-160"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/113.2.347"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1086\/342359"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10422"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-0004.2003.00138.x"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1177\/088307389601100114"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-979781"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20665"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20879"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2635267100"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg184"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M313504200"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M410508200"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M506216200"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi440"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1645-05.2005"},{"key":"e_1_2_6_24_2","volume-title":"Merritt's textbook of neurology","author":"Merritt HH","year":"2000"},{"key":"e_1_2_6_25_2","volume-title":"Neurology in clinical practice","author":"Bradley WG","year":"2004"},{"key":"e_1_2_6_26_2","volume-title":"Harrison's principles of internal medicine","author":"Braunwald E","year":"2001"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80272-X"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.280.5369.1610"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200420138"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/cne.20196"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000048207.28790.25"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/0168-0102(95)00895-9"},{"key":"e_1_2_6_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/cne.20090"},{"key":"e_1_2_6_34_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004150050503"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00221-003-1393-9"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2004.07.092"}],"container-title":["Annals of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fana.20888","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ana.20888","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T16:28:39Z","timestamp":1696955319000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ana.20888"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,6,26]]},"references-count":35,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2006,7]]}},"alternative-id":["10.1002\/ana.20888"],"URL":"https:\/\/doi.org\/10.1002\/ana.20888","archive":["Portico"],"relation":{},"ISSN":["0364-5134","1531-8249"],"issn-type":[{"value":"0364-5134","type":"print"},{"value":"1531-8249","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,6,26]]}}}