{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:11:17Z","timestamp":1792033877030,"version":"4.4.0"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2024,3,27]],"date-time":"2024-03-27T00:00:00Z","timestamp":1711497600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Judy Seltzer Levenson Memorial Fund","award":["5R01NS105755"],"award-info":[{"award-number":["5R01NS105755"]}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DO 2386\/1-1"],"award-info":[{"award-number":["DO 2386\/1-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,9,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Biallelic SORD mutations cause one of the most frequent forms of recessive hereditary neuropathy, estimated to affect \u223c10 000 patients in North America and Europe alone. Pathogenic SORD loss-of-function changes in the encoded enzyme sorbitol dehydrogenase result in abnormally high sorbitol levels in cells and serum. How sorbitol accumulation leads to peripheral neuropathy remains to be elucidated.<\/jats:p>\n                  <jats:p>A reproducible animal model for SORD neuropathy is essential to illuminate the pathogenesis of SORD deficiency and for preclinical studies of potential therapies. Therefore, we have generated a Sord knockout (KO), Sord\u2212\/\u2212, Sprague Dawley rat, to model the human disease and to investigate the pathophysiology underlying SORD deficiency.<\/jats:p>\n                  <jats:p>We have characterized the phenotype in these rats with a battery of behavioural tests as well as biochemical, physiological and comprehensive histological examinations. Sord\u2212\/\u2212 rats had remarkably increased levels of sorbitol in serum, CSF and peripheral nerve. Moreover, serum from Sord\u2212\/\u2212 rats contained significantly increased levels of neurofilament light chain, an established biomarker for axonal degeneration. Motor performance significantly declined in Sord\u2212\/\u2212 animals starting at \u223c7 months of age. Gait analysis evaluated with video motion-tracking confirmed abnormal gait patterns in the hindlimbs. Motor nerve conduction velocities of the tibial nerves were slowed. Light and electron microscopy of the peripheral nervous system revealed degenerating myelinated axons, de- and remyelinated axons, and a likely pathognomonic finding\u2014enlarged \u2018ballooned\u2019 myelin sheaths. These findings mainly affected myelinated motor axons; myelinated sensory axons were largely spared.<\/jats:p>\n                  <jats:p>In summary, Sord\u2212\/\u2212 rats develop a motor-predominant neuropathy that closely resembles the human phenotype. Our studies revealed novel significant aspects of SORD deficiency, and this model will lead to an improved understanding of the pathophysiology and the therapeutic options for SORD neuropathy.<\/jats:p>","DOI":"10.1093\/brain\/awae079","type":"journal-article","created":{"date-parts":[[2024,3,26]],"date-time":"2024-03-26T18:54:51Z","timestamp":1711479291000},"page":"3131-3143","source":"Crossref","is-referenced-by-count":11,"title":["SORD-deficient rats develop a motor-predominant peripheral neuropathy unveiling novel pathophysiological insights"],"prefix":"10.1093","volume":"147","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5669-7415","authenticated-orcid":false,"given":"Adriana P","family":"Rebelo","sequence":"first","affiliation":[{"name":"Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine , Miami, FL 33136 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clemer","family":"Abad","sequence":"additional","affiliation":[{"name":"Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine , Miami, FL 33136 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5320-9807","authenticated-orcid":false,"given":"Maike F","family":"Dohrn","sequence":"additional","affiliation":[{"name":"Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine , Miami, FL 33136 ,","place":["USA"]},{"name":"Department of Neurology, Medical Faculty, RWTH Aachen University , Aachen 52074 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian J","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Perelman School of Medicine at the University of Pennsylvania , Philadelphia, PA 19104 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ethan K","family":"Tieu","sequence":"additional","affiliation":[{"name":"Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine , Miami, FL 33136 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Medina","sequence":"additional","affiliation":[{"name":"Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine , Miami, FL 33136 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Yanick","sequence":"additional","affiliation":[{"name":"Graduate Program in Neuroscience, University of Miami Miller School of Medicine , Miami, FL 33136 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyu","family":"Huang","sequence":"additional","affiliation":[{"name":"Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine , Miami, FL 33136 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendan","family":"Zotter","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Perelman School of Medicine at the University of Pennsylvania , Philadelphia, PA 19104 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan I","family":"Young","sequence":"additional","affiliation":[{"name":"Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine , Miami, FL 33136 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Saporta","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Miami Miller School of Medicine , Miami, FL 33136 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven S","family":"Scherer","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Perelman School of Medicine at the University of Pennsylvania , Philadelphia, PA 19104 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherina","family":"Walz","sequence":"additional","affiliation":[{"name":"Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine , Miami, FL 33136 ,","place":["USA"]},{"name":"IQUIBICEN\u2014CONICET, Faculty of Exact and Natural Sciences\u2014University of Buenos Aires , Buenos Aires C1428EG4 ,","place":["Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8498-5235","authenticated-orcid":false,"given":"Stephan","family":"Zuchner","sequence":"additional","affiliation":[{"name":"Dr. John T. Macdonald Foundation Department of Human Genetics and John P. 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