{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:09:19Z","timestamp":1787022559880,"version":"build-2736575974"},"reference-count":36,"publisher":"Walter de Gruyter GmbH","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,7,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Niemann-Pick type C disease (NPC) is a rare human disease, with limited effective treatment options. Most cases of NPC disease are associated with inactivating mutations of the\n                    <jats:italic>NPC1<\/jats:italic>\n                    gene. However, cellular and molecular mechanisms responsible for the\n                    <jats:italic>NPC1<\/jats:italic>\n                    pathogenesis remain poorly defined. This is partly due to the lack of a suitable animal model to monitor the disease progression. In this study, we used CRISPR to construct an\n                    <jats:italic>NPC1<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    zebrafish model, which faithfully reproduced the cardinal pathological features of this disease. In contrast to the wild type (WT), the deletion of\n                    <jats:italic>NPC1<\/jats:italic>\n                    alone caused significant hepatosplenomegaly, ataxia, Purkinje cell death, increased lipid storage, infertility and reduced body length and life span. Most of the\n                    <jats:italic>NPC1<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    zebrafish died within the first month post fertilization, while the remaining specimens developed slower than the WT and died before reaching 8 months of age. Filipin-stained hepatocytes of the\n                    <jats:italic>NPC1<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    zebrafish were clear, indicating abnormal accumulation of unesterified cholesterol. Lipid profiling showed a significant difference between\n                    <jats:italic>NPC1<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    and WT zebrafish. An obvious accumulation of seven sphingolipids was detected in livers of\n                    <jats:italic>NPC1<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    zebrafish. In summary, our results provide a valuable model system that could identify promising therapeutic targets and treatments for the NPC disease.\n                  <\/jats:p>","DOI":"10.1515\/hsz-2018-0118","type":"journal-article","created":{"date-parts":[[2018,6,13]],"date-time":"2018-06-13T18:51:14Z","timestamp":1528915874000},"page":"903-910","source":"Crossref","is-referenced-by-count":29,"title":["Model construction of Niemann-Pick type C disease in zebrafish"],"prefix":"10.1515","volume":"399","author":[{"given":"Yusheng","family":"Lin","sequence":"first","affiliation":[{"name":"State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences , Donghu South Road 7# , Wuhan 430072 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolian","family":"Cai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences , Donghu South Road 7# , Wuhan 430072 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guiping","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences , Donghu South Road 7# , Wuhan 430072 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Ouyang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences , Donghu South Road 7# , Wuhan 430072 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Cao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences , Donghu South Road 7# , Wuhan 430072 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2018,6,20]]},"reference":[{"key":"2023040406464464187_j_hsz-2018-0118_ref_001_w2aab3b7c26b1b6b1ab2b1b1Aa","doi-asserted-by":"crossref","unstructured":"Cao, H., Zhou, L., Zhang, Y.Z., Wei, Q.W., Chen, X.H., and Gui, J.F. 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