{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:08:41Z","timestamp":1791925721549,"version":"4.3.4"},"reference-count":56,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2019,7,23]],"date-time":"2019-07-23T00:00:00Z","timestamp":1563840000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education, Culture, Sports, Science and Technology, Japan","award":["22580341"],"award-info":[{"award-number":["22580341"]}]},{"name":"Ministry of Education, Culture, Sports, Science and Technology, Japan","award":["26450414"],"award-info":[{"award-number":["26450414"]}]},{"name":"Ministry of Education, Culture, Sports, Science and Technology, Japan","award":["15K18368"],"award-info":[{"award-number":["15K18368"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>WW domain-containing oxidoreductase (Wwox) is a putative tumor suppressor. Several germline mutations of Wwox have been associated with infant neurological disorders characterized by epilepsy, growth retardation, and early death. Less is known, however, about the pathological link between Wwox mutations and these disorders or the physiological role of Wwox in brain development. In this study, we examined age-related expression and histological localization of Wwox in forebrains as well as the effects of loss of function mutations in the Wwox gene in the immature cortex of a rat model of lethal dwarfism with epilepsy (lde\/lde). Immunostaining revealed that Wwox is expressed in neurons, astrocytes, and oligodendrocytes. lde\/lde cortices were characterized by a reduction in neurite growth without a reduced number of neurons, severe reduction in myelination with a reduced number of mature oligodendrocytes, and a reduction in cell populations of astrocytes and microglia. These results indicate that Wwox is essential for normal development of neurons and glial cells in the cerebral cortex.<\/jats:p>","DOI":"10.3390\/ijms20143596","type":"journal-article","created":{"date-parts":[[2019,7,23]],"date-time":"2019-07-23T10:44:51Z","timestamp":1563878691000},"page":"3596","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Loss of Wwox Causes Defective Development of Cerebral Cortex with Hypomyelination in a Rat Model of Lethal Dwarfism with Epilepsy"],"prefix":"10.3390","volume":"20","author":[{"given":"Yuki","family":"Tochigi","sequence":"first","affiliation":[{"name":"Laboratory of Veterinary Physiology, School of Veterinary Medicine, Faculty of Veterinary Science, Nippon Veterinary and Life Science University, Musashino-shi, Tokyo 180-8602, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Takamatsu","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Physiology, School of Veterinary Medicine, Faculty of Veterinary Science, Nippon Veterinary and Life Science University, Musashino-shi, Tokyo 180-8602, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Nakane","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Physiology, School of Veterinary Medicine, Faculty of Veterinary Science, Nippon Veterinary and Life Science University, Musashino-shi, Tokyo 180-8602, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rika","family":"Nakai","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Physiology, School of Veterinary Medicine, Faculty of Veterinary Science, Nippon Veterinary and Life Science University, Musashino-shi, Tokyo 180-8602, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2859-0423","authenticated-orcid":false,"given":"Kentaro","family":"Katayama","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Physiology, School of Veterinary Medicine, Faculty of Veterinary Science, Nippon Veterinary and Life Science University, Musashino-shi, Tokyo 180-8602, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroetsu","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Physiology, School of Veterinary Medicine, Faculty of Veterinary Science, Nippon Veterinary and Life Science University, Musashino-shi, Tokyo 180-8602, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,7,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.molmed.2006.11.006","article-title":"WW domain-containing oxidoreductase: A candidate tumor suppressor","volume":"13","author":"Chang","year":"2007","journal-title":"Trends Mol. 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