{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:05:29Z","timestamp":1790399129639,"version":"4.1.0"},"reference-count":20,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,3,3]],"date-time":"2015-03-03T00:00:00Z","timestamp":1425340800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK093386"],"award-info":[{"award-number":["DK093386"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK079209"],"award-info":[{"award-number":["DK079209"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2015,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">ATP7A<\/jats:styled-content> is a copper\u2010transporting P\u2010type <jats:styled-content style=\"fixed-case\">ATPase<\/jats:styled-content> that is essential for cellular copper homeostasis. Loss\u2010of\u2010function mutations in the <jats:italic><jats:styled-content style=\"fixed-case\">ATP7A<\/jats:styled-content><\/jats:italic> gene result in Menkes disease, a fatal neurodegenerative disorder resulting in seizures, hypotonia and failure to thrive, due to systemic copper deficiency. Most recently, rare missense mutations in <jats:italic><jats:styled-content style=\"fixed-case\">ATP7A<\/jats:styled-content><\/jats:italic> that do not impact systemic copper homeostasis have been shown to cause X\u2010linked spinal muscular atrophy type 3 (<jats:styled-content style=\"fixed-case\">SMAX3<\/jats:styled-content>), a distal hereditary motor neuropathy. An understanding of the mechanistic and pathophysiological basis of <jats:styled-content style=\"fixed-case\">SMAX3<\/jats:styled-content> is currently lacking, in part because the disease\u2010causing mutations have been shown to confer both loss\u2010 and gain\u2010of\u2010function properties to <jats:styled-content style=\"fixed-case\">ATP7A<\/jats:styled-content>, and because there is currently no animal model of the disease. In this study, the <jats:italic>Atp7a<\/jats:italic> gene was specifically deleted in the motor neurons of mice, resulting in a degenerative phenotype consistent with the clinical features in affected patients with <jats:styled-content style=\"fixed-case\">SMAX3<\/jats:styled-content>, including the progressive deterioration of gait, age\u2010dependent muscle atrophy, denervation of neuromuscular junctions and a loss of motor neuron cell bodies. Taken together, these data reveal autonomous requirements for <jats:styled-content style=\"fixed-case\">ATP7A<\/jats:styled-content> that reveal essential roles for copper in the maintenance and function of the motor neuron, and suggest that <jats:styled-content style=\"fixed-case\">SMAX3<\/jats:styled-content> is caused by a loss of <jats:styled-content style=\"fixed-case\">ATP7A<\/jats:styled-content> function that specifically impacts the spinal motor neuron. Copyright \u00a9 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.4511","type":"journal-article","created":{"date-parts":[[2015,1,30]],"date-time":"2015-01-30T02:46:41Z","timestamp":1422586001000},"page":"241-250","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["X\u2010linked spinal muscular atrophy in mice caused by autonomous loss of ATP7A in the motor neuron"],"prefix":"10.1002","volume":"236","author":[{"given":"Victoria L","family":"Hodgkinson","sequence":"first","affiliation":[{"name":"Department of Biochemistry University of Missouri  Columbia MO USA"},{"name":"Christopher S Bond Life Science Center University of Missouri  Columbia MO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffery M","family":"Dale","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences University of Missouri  Columbia MO USA"},{"name":"Christopher S Bond Life Science Center 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