{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T21:17:04Z","timestamp":1793654224804,"version":"4.5.1"},"reference-count":39,"publisher":"National Academy of Sciences","issue":"8","license":[{"start":{"date-parts":[[2009,8,24]],"date-time":"2009-08-24T00:00:00Z","timestamp":1251072000000},"content-version":"vor","delay-in-days":181,"URL":"http:\/\/www.pnas.org\/site\/misc\/userlicense.xhtml"}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,2,24]]},"abstract":"<jats:p>\n                    Canine degenerative myelopathy (DM) is a fatal neurodegenerative disease prevalent in several dog breeds. Typically, the initial progressive upper motor neuron spastic and general proprioceptive ataxia in the pelvic limbs occurs at 8 years of age or older. If euthanasia is delayed, the clinical signs will ascend, causing flaccid tetraparesis and other lower motor neuron signs. DNA samples from 38 DM-affected Pembroke Welsh corgi cases and 17 related clinically normal controls were used for genome-wide association mapping, which produced the strongest associations with markers on CFA31 in a region containing the canine\n                    <jats:italic>SOD1<\/jats:italic>\n                    gene.\n                    <jats:italic>SOD1<\/jats:italic>\n                    was considered a regional candidate gene because mutations in human\n                    <jats:italic>SOD1<\/jats:italic>\n                    can cause amyotrophic lateral sclerosis (ALS), an adult-onset fatal paralytic neurodegenerative disease with both upper and lower motor neuron involvement. The resequencing of\n                    <jats:italic>SOD1<\/jats:italic>\n                    in normal and affected dogs revealed a G to A transition, resulting in an E40K missense mutation. Homozygosity for the A allele was associated with DM in 5 dog breeds: Pembroke Welsh corgi, Boxer, Rhodesian ridgeback, German Shepherd dog, and Chesapeake Bay retriever. Microscopic examination of spinal cords from affected dogs revealed myelin and axon loss affecting the lateral white matter and neuronal cytoplasmic inclusions that bind anti-superoxide dismutase 1 antibodies. These inclusions are similar to those seen in spinal cord sections from ALS patients with\n                    <jats:italic>SOD1<\/jats:italic>\n                    mutations. Our findings identify canine DM to be the first recognized spontaneously occurring animal model for ALS.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0812297106","type":"journal-article","created":{"date-parts":[[2009,2,2]],"date-time":"2009-02-02T21:35:01Z","timestamp":1233610501000},"page":"2794-2799","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":237,"title":["Genome-wide association analysis reveals a\n                    <i>SOD1<\/i>\n                    mutation in canine degenerative myelopathy that resembles amyotrophic lateral sclerosis"],"prefix":"10.1073","volume":"106","author":[{"given":"Tomoyuki","family":"Awano","sequence":"first","affiliation":[{"name":"Departments of aVeterinary Pathobiology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary S.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Departments of aVeterinary Pathobiology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire M.","family":"Wade","sequence":"additional","affiliation":[{"name":"Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge MA 02141;"},{"name":"Center for Human Genetic Research, Massachusetts General Hospital, 185 Cambridge Street, Boston MA 02114;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin L.","family":"Katz","sequence":"additional","affiliation":[{"name":"Departments of aVeterinary Pathobiology and"},{"name":"Mason Eye Institute, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gayle C.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Departments of aVeterinary Pathobiology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy F.","family":"Taylor","sequence":"additional","affiliation":[{"name":"Division of Animal Sciences, University of Missouri, Columbia MO 65211;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Perloski","sequence":"additional","affiliation":[{"name":"Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge MA 02141;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tara","family":"Biagi","sequence":"additional","affiliation":[{"name":"Broad Institute of Harvard and Massachusetts Institute of Technology, 7 Cambridge Center, Cambridge MA 02141;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izabella","family":"Baranowska","sequence":"additional","affiliation":[{"name":"Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Biomedical Center, Box 597, SE-751 24 Uppsala, Sweden;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam","family":"Long","sequence":"additional","affiliation":[{"name":"Section of Neurology and Neurosurgery, University of Pennsylvania, Philadelphia, PA 19104;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip A.","family":"March","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Tufts University, North Grafton, MA 01536;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha J.","family":"Olby","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, North Carolina State University, Raleigh, NC 27606;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. 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