{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:30:06Z","timestamp":1790713806850,"version":"4.1.0"},"reference-count":69,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2016,7,5]],"date-time":"2016-07-05T00:00:00Z","timestamp":1467676800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001658","name":"Minerva Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001658","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":[[2016,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Great interest has been shown in understanding the pathology of Gaucher disease (\n                    <jats:styled-content style=\"fixed-case\">GD<\/jats:styled-content>\n                    ) due to the recently discovered genetic relationship with Parkinson's disease. For such studies, suitable animal models of\n                    <jats:styled-content style=\"fixed-case\">GD<\/jats:styled-content>\n                    are required. Chemical induction of\n                    <jats:styled-content style=\"fixed-case\">GD<\/jats:styled-content>\n                    by inhibition of acid \u03b2\u2010glucosidase (\n                    <jats:styled-content style=\"fixed-case\">GCase<\/jats:styled-content>\n                    ) using the irreversible inhibitor conduritol B\u2010epoxide (\n                    <jats:styled-content style=\"fixed-case\">CBE<\/jats:styled-content>\n                    ) is particularly attractive, although few systematic studies examining the effect of\n                    <jats:styled-content style=\"fixed-case\">CBE<\/jats:styled-content>\n                    on the development of symptoms associated with neurological forms of\n                    <jats:styled-content style=\"fixed-case\">GD<\/jats:styled-content>\n                    have been performed. We now demonstrate a correlation between the amount of\n                    <jats:styled-content style=\"fixed-case\">CBE<\/jats:styled-content>\n                    injected into mice and levels of accumulation of the\n                    <jats:styled-content style=\"fixed-case\">GD<\/jats:styled-content>\n                    substrates, glucosylceramide and glucosylsphingosine, and show that disease pathology, indicated by altered levels of pathological markers, depends on both the levels of accumulated lipids and the time at which their accumulation begins. Gene array analysis shows a remarkable similarity in the gene expression profiles of\n                    <jats:styled-content style=\"fixed-case\">CBE<\/jats:styled-content>\n                    \u2010treated mice and a genetic\n                    <jats:styled-content style=\"fixed-case\">GD<\/jats:styled-content>\n                    mouse model, the\n                    <jats:italic>Gba<\/jats:italic>\n                    <jats:sup>flox\/flox<\/jats:sup>\n                    ;nestin\u2010Cre mouse, with 120 of the 144 genes up\u2010regulated in\n                    <jats:styled-content style=\"fixed-case\">CBE<\/jats:styled-content>\n                    \u2010treated mice also up\u2010regulated in\n                    <jats:italic>Gba<\/jats:italic>\n                    <jats:sup>flox\/flox<\/jats:sup>\n                    ;nestin\u2010Cre mice. We also demonstrate that various aspects of neuropathology and some behavioural abnormalities can be arrested upon cessation of\n                    <jats:styled-content style=\"fixed-case\">CBE<\/jats:styled-content>\n                    treatment during a specific time window. Together, our data demonstrate that injection of mice with\n                    <jats:styled-content style=\"fixed-case\">CBE<\/jats:styled-content>\n                    provides a rapid and relatively easy way to induce symptoms typical of neuronal forms of\n                    <jats:styled-content style=\"fixed-case\">GD<\/jats:styled-content>\n                    . This is particularly useful when examining the role of specific biochemical pathways in\n                    <jats:styled-content style=\"fixed-case\">GD<\/jats:styled-content>\n                    pathology, since\n                    <jats:styled-content style=\"fixed-case\">CBE<\/jats:styled-content>\n                    can be injected into mice defective in components of putative pathological pathways, alleviating the need for time\u2010consuming crossing of mice. Copyright \u00a9 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.\n                  <\/jats:p>","DOI":"10.1002\/path.4751","type":"journal-article","created":{"date-parts":[[2016,5,28]],"date-time":"2016-05-28T08:26:37Z","timestamp":1464423997000},"page":"496-509","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":78,"title":["Delineating pathological pathways in a chemically induced mouse model of Gaucher disease"],"prefix":"10.1002","volume":"239","author":[{"given":"Ayelet","family":"Vardi","sequence":"first","affiliation":[{"name":"Department of Biological Chemistry Weizmann Institute of Science  Rehovot Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hila","family":"Zigdon","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry Weizmann Institute of Science  Rehovot Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Meshcheriakova","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry Weizmann Institute of Science  Rehovot Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9s D","family":"Klein","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry Weizmann Institute of Science  Rehovot Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Yaacobi","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry Weizmann Institute of Science  Rehovot Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raya","family":"Eilam","sequence":"additional","affiliation":[{"name":"Department of Veterinary Resources Weizmann Institute of Science  Rehovot Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon M","family":"Kenwood","sequence":"additional","affiliation":[{"name":"School of Biology and Petit Institute for Bioengineering and Bioscience Georgia Institute of Technology  Atlanta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahad A","family":"Rahim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Massaro","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"Alfred H","family":"Merrill","sequence":"additional","affiliation":[{"name":"School of Biology and Petit Institute for Bioengineering and Bioscience Georgia Institute of Technology  Atlanta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Einat B","family":"Vitner","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry Weizmann Institute of Science  Rehovot Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony H","family":"Futerman","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry Weizmann Institute of Science  Rehovot Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,7,5]]},"reference":[{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1423"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20676"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1517\/14728222.2014.981530"},{"key":"e_1_2_7_6_1","first-page":"3635","volume-title":"The Metabolic and Molecular Bases of Inherited Disease","author":"Beutler E","year":"2001"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0901281"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3449"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr019"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt468"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq273"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aws095"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp061"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.14348\/molcells.2015.0117"},{"key":"e_1_2_7_15_1","first-page":"1189","article-title":"From sheep to mice to cells: tools for the study of the sphingolipidoses","volume":"2014","author":"Zigdon H","year":"1841","journal-title":"Biochim Biophys Acta"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.008185"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0708086104"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(75)90286-7"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-4165(81)90276-2"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)00084-2"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.07-102715"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.03.001"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0163-7827(85)90011-6"},{"key":"e_1_2_7_24_1","article-title":"Substrate compositional variation with tissue\/region and Gba1 mutations in mouse models\u2013implications for Gaucher disease","volume":"8","author":"Sun Y","year":"2013","journal-title":"PLoS One"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M600344-JLR200"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0120194"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1400768111"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-016-0570-2"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2014.00404"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2012.00046"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2015.6307"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2013.12.003"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-8-140"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-4165(79)90134-X"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M610544200"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.463562"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cwn041"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)37024-3"},{"key":"e_1_2_7_39_1","article-title":"Visualization of active glucocerebrosidase in rodent brain with high spatial resolution following in situ labeling with fluorescent activity based probes","volume":"10","author":"Chao DHM","year":"2015","journal-title":"PLoS One"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1006\/mthe.2002.0650"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2014.12.169"},{"key":"e_1_2_7_42_1","first-page":"255","article-title":"Gaucher disease in mice induced by conduritol\u2010B\u2010epoxide: morphologic features","volume":"101","author":"Adachi M","year":"1977","journal-title":"Arch Pathol Lab Med"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1978.tb12395.x"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-4165(79)90133-8"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1979.tb04582.x"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02537244"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02535529"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(88)80693-4"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117160"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117997"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.1998.00145.x"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2004.08.031"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2008.01.013"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2009.06.009"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2010.12.014"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.194.Supp.186.14"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2004.04.011"},{"key":"e_1_2_7_58_1","doi-asserted-by":"crossref","unstructured":"WongK.Neuropathological aspects of Gaucher disease. InGaucher Disease Futerman AH Zimran A (eds). Taylor & Francis: Boca Raton FL 2007; 225\u2013248.","DOI":"10.1201\/9781420005509.ch13"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1982.tb07950.x"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00690463"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.1985.tb00229.x"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410200208"},{"key":"e_1_2_7_63_1","first-page":"A427","article-title":"Glucosylsphingosine accumulation in patients with Gaucher disease","volume":"65","author":"Orvisky E","year":"1999","journal-title":"Am J Hum Genet"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-200008000-00018"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1096-7192(02)00117-8"},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M300212200"},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2004.09.004"},{"key":"e_1_2_7_68_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3030377"},{"key":"e_1_2_7_69_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.414714"},{"key":"e_1_2_7_70_1","doi-asserted-by":"publisher","DOI":"10.1139\/y59-099"},{"key":"e_1_2_7_71_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-9-488"}],"container-title":["The Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpath.4751","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpath.4751","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.4751","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T14:24:05Z","timestamp":1760970245000},"score":1,"resource":{"primary":{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/10.1002\/path.4751"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,7,5]]},"references-count":69,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2016,8]]}},"alternative-id":["10.1002\/path.4751"],"URL":"https:\/\/doi.org\/10.1002\/path.4751","archive":["Portico"],"relation":{},"ISSN":["0022-3417","1096-9896"],"issn-type":[{"value":"0022-3417","type":"print"},{"value":"1096-9896","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,7,5]]},"assertion":[{"value":"2016-03-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-05-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-07-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}