{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:45:51Z","timestamp":1787013951570,"version":"build-2736575974"},"reference-count":64,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2016,8,23]],"date-time":"2016-08-23T00:00:00Z","timestamp":1471910400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"The McLaughlin Research Institute"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology of the Cell"],"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background Information<\/jats:title>\n                    <jats:p>\n                      Vacuolation of the central nervous system (CNS) is observed in patients with transmissible spongiform encephalopathy, HIV\u2010related encephalopathy and some inherited diseases, but the underlying cellular mechanisms remain poorly understood. Mice lacking the mahogunin ring finger\u20101 (MGRN1) E3 ubiquitin ligase develop progressive, widespread spongiform degeneration of the CNS. MGRN1 ubiquitinates and regulates tumour susceptibility gene 101 (TSG101), a central component of the endosomal trafficking machinery. As loss of MGRN1 is predicted to cause partial TSG101 loss\u2010of\u2010function, we hypothesised that CNS vacuolation in\n                      <jats:italic>Mgrn1<\/jats:italic>\n                      null mice may be caused by the accumulation of multi\u2010cisternal endosome\u2010like \u2018class E\u2019 vacuolar protein sorting (vps) compartments similar to those observed in\n                      <jats:italic>Tsg101<\/jats:italic>\n                      \u2010depleted cells in culture.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      To test this hypothesis,\n                      <jats:italic>Tsg101<\/jats:italic>\n                      was deleted from mature oligodendroglia\n                      <jats:italic>in vivo<\/jats:italic>\n                      . This resulted in severe spongiform encephalopathy, histopathologically similar to that observed in\n                      <jats:italic>Mgrn1<\/jats:italic>\n                      null mutant mice but with a more rapid onset. Vacuoles in the brains of\n                      <jats:italic>Tsg101<\/jats:italic>\n                      \u2010deleted and\n                      <jats:italic>Mgrn1<\/jats:italic>\n                      mutant mice labelled with endosomal markers, consistent with an endosomal origin. Vacuoles in the brains of mice inoculated with Rocky Mountain Laboratory (RML) prions did not label with these markers, indicating a different origin, consistent with previously published studies that indicate RML prions have a primary effect on neurons and cause vacuolation in an MGRN1\u2010independent manner. Oligodendroglial deletion of\n                      <jats:italic>Rab7<\/jats:italic>\n                      , which mediates late endosome\u2010to\u2010lysosome trafficking and autophagosome\u2013lysosome fusion, did not cause spongiform change.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our data suggest that the formation of multi\u2010cisternal \u2018class E\u2019 vps endosomal structures in oligodendroglia leads to vacuolation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>This work provides the first evidence that disrupting multi\u2010vesicular body formation in oligodendroglia can cause white matter vacuolation and demyelination. HIV is known to hijack the endosomal sorting machinery, suggesting that HIV infection of the CNS may also act through this pathway to cause encephalopathy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/boc.201600014","type":"journal-article","created":{"date-parts":[[2016,7,13]],"date-time":"2016-07-13T01:04:49Z","timestamp":1468371889000},"page":"324-337","source":"Crossref","is-referenced-by-count":18,"title":["Oligodendroglial deletion of ESCRT\u2010I component TSG101 causes spongiform encephalopathy"],"prefix":"10.1111","volume":"108","author":[{"given":"Will P.","family":"Walker","sequence":"first","affiliation":[{"name":"McLaughlin Research Institute  Great Falls MT 59405 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abby","family":"Oehler","sequence":"additional","affiliation":[{"name":"Department of Pathology Institute for Neurodegenerative Diseases University of California  San Francisco CA 94143 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aimee L.","family":"Edinger","sequence":"additional","affiliation":[{"name":"Department of Developmental and Cell Biology University of California  Irvine CA 92697 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kay\u2010Uwe","family":"Wagner","sequence":"additional","affiliation":[{"name":"Eppley Institute for Research in Cancer and Allied Diseases University of Nebraska Medical Center  Omaha NE 68198 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa M.","family":"Gunn","sequence":"additional","affiliation":[{"name":"McLaughlin Research Institute  Great Falls MT 59405 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,8,23]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-014-1735-8"},{"key":"e_1_2_10_3_1","first-page":"374","article-title":"Spongiform encephalopathy in AIDS dementia complex: report of five cases","volume":"2","author":"Artigas J.","year":"1989","journal-title":"J. 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