{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T15:10:43Z","timestamp":1784214643395,"version":"3.55.0"},"reference-count":57,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100001250","name":"Morris Animal Foundation","doi-asserted-by":"publisher","award":["D24EQ\u2010056"],"award-info":[{"award-number":["D24EQ\u2010056"]}],"id":[{"id":"10.13039\/100001250","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016749","name":"UC Davis Center for Equine Health","doi-asserted-by":"publisher","award":["24\u201004"],"award-info":[{"award-number":["24\u201004"]}],"id":[{"id":"10.13039\/100016749","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014840","name":"American Quarter Horse Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014840","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["beva.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Equine Veterinary Journal"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Equine neuroaxonal dystrophy\/degenerative myeloencephalopathy (eNAD\/EDM) is the second most common diagnosis of spinal ataxia in horses in the United States. The disease develops due to a combination of vitamin E deficiency and an unknown genetic risk factor(s), and there currently is no effective treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>We performed transcriptomic profiling of the liver and small intestine of horses with and without eNAD\/EDM, as both tissues are the main locations for absorption, metabolism,\u00a0and delivery of vitamin E to the nervous system.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study Design<\/jats:title>\n                    <jats:p>Case\u2010control exploratory study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Postmortem\u2010confirmed cases of eNAD\/EDM were compared to horses that had eNAD\/EDM excluded at necropsy and were euthanised for either non\u2010neurologic disease or for cervical vertebral compressive myelopathy (CVCM), which were included due to the logistical challenge of obtaining control horses that have undergone a full neuropathologic review. RNA was isolated from frozen liver (eNAD\/EDM\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200934, non\u2010eNAD\/EDM\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200927) and small intestinal (eNAD\/EDM\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200918, non\u2010eNAD\/EDM\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200918) samples. Gene expression was compared between groups using a linear model, adjusting for age, breed, and RNA integrity score.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      No genes were differentially expressed at\n                      <jats:italic>p<\/jats:italic>\n                      <jats:sub>FDR<\/jats:sub>\n                      &lt;0.05 in either tissue between eNAD\/EDM and non\u2010eNAD\/EDM horses. However, one of the top genes,\n                      <jats:italic>NPC1L1<\/jats:italic>\n                      , was upregulated in the liver of horses with eNAD\/EDM (log\n                      <jats:sub>2<\/jats:sub>\n                      FC\u2009=\u20090.93,\n                      <jats:italic>p<\/jats:italic>\n                      <jats:sub>unadjusted<\/jats:sub>\n                      &lt; 0.05). In the small intestine, 747 genes were differentially expressed (\n                      <jats:italic>p<\/jats:italic>\n                      <jats:sub>unadjusted<\/jats:sub>\n                      \u2009&lt;0.05), including two genes that were markedly downregulated in both tissues. These genes have high sequence homology to\n                      <jats:italic>LGALS9<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main Limitations<\/jats:title>\n                    <jats:p>Non\u2010neurologic control numbers were limited. Tissues were collected at the time of euthanasia and therefore may not capture biological processes that were occurring at the time the neurological damage developed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Processes related to both cholesterol transport and autophagy may be altered in horses with eNAD\/EDM. Two new candidate genes for eNAD\/EDM,\n                      <jats:italic>NPC1L1<\/jats:italic>\n                      and\n                      <jats:italic>LGALS9<\/jats:italic>\n                      , were identified for further investigation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/evj.70216","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T14:56:13Z","timestamp":1784213773000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Altered gene expression in the liver and small intestine of horses with equine neuroaxonal dystrophy"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5538-0675","authenticated-orcid":false,"given":"Stephanie","family":"Ryan","sequence":"first","affiliation":[{"name":"Department of Population Health and Reproduction University of California Davis  Davis California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blythe","family":"Durbin\u2010Johnson","sequence":"additional","affiliation":[{"name":"Bioinformatics Core Facility, Genome Center, University of California Davis  Davis California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Woolard","sequence":"additional","affiliation":[{"name":"Department of Pathology Microbiology and Immunology, University of California Davis  Davis California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew D.","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Population Medicine and Diagnostic Sciences Section of Anatomic Pathology, College of Veterinary Medicine, Cornell University  New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5924-0234","authenticated-orcid":false,"given":"Carrie J.","family":"Finno","sequence":"additional","affiliation":[{"name":"Department of Population Health and Reproduction University of California Davis  Davis California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,16]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.cveq.2022.04.003","article-title":"Equine neuroaxonal dystrophy and degenerative myeloencephalopathy","volume":"38","author":"Finno CJ","year":"2022","journal-title":"Vet Clin N Am Equine Pract"},{"key":"e_1_2_12_3_1","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1111\/jvim.13618","article-title":"Blood and cerebrospinal fluid \u03b1\u2010tocopherol and selenium concentrations in neonatal foals with neuroaxonal dystrophy","volume":"29","author":"Finno CJ","year":"2015","journal-title":"J Vet Intern 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