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Model construction of Niemann-Pick type C disease in zebrafish
Lin, Yusheng; Cai, Xiaolian; Wang, Guiping; Ouyang, Gang; Cao, Hong
2018-08-01
Source PublicationBIOLOGICAL CHEMISTRY
ISSN1431-6730
Volume399Issue:8Pages:903-910
Abstract

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 NPC1 gene. However, cellular and molecular mechanisms responsible for the NPC1 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 NPC1(-/-) zebrafish model, which faithfully reproduced the cardinal pathological features of this disease. In contrast to the wild type (WT), the deletion of NPC1 alone caused significant hepatosplenomegaly, ataxia, Purkinje cell death, increased lipid storage, infertility and reduced body length and life span. Most of the NPC1(-/-) 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 NPC1(-/-) zebrafish were clear, indicating abnormal accumulation of unesterified cholesterol. Lipid profiling showed a significant difference between NPC1(-)/(-) and WT zebrafish. An obvious accumulation of seven sphingolipids was detected in livers of NPC1(-/-) zebrafish. In summary, our results provide a valuable model system that could identify promising therapeutic targets and treatments for the NPC disease.

Keywordcholesterol CRISPR/Cas9 NPC1 zebrafish
DOI10.1515/hsz-2018-0118
Funding OrganizationState Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology
Indexed BySCI
Language英语
Funding ProjectState Key Laboratory of Freshwater Ecology and Biotechnology[2012FB04]
WOS Research AreaBiochemistry & Molecular Biology
WOS SubjectBiochemistry & Molecular Biology
WOS IDWOS:000438949700009
WOS KeywordSTEROL-SENSING DOMAIN ; TRANSGENIC ZEBRAFISH ; NPC1 PROTEIN ; IDENTIFICATION ; MUTATIONS ; CHOLESTEROL ; NEURODEGENERATION ; HOMEOSTASIS ; PHENOTYPE ; NEURONS
PublisherWALTER DE GRUYTER GMBH
Funding OrganizationState Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology ; State Key Laboratory of Freshwater Ecology and Biotechnology
Citation statistics
Cited Times:7[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.ihb.ac.cn/handle/342005/34544
Collection水生生物分子与细胞生物学研究中心_期刊论文
Corresponding AuthorCao, Hong
AffiliationChinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Donghu South Rd 7, Wuhan 430072, Hubei, Peoples R China
Recommended Citation
GB/T 7714
Lin, Yusheng,Cai, Xiaolian,Wang, Guiping,et al. Model construction of Niemann-Pick type C disease in zebrafish[J]. BIOLOGICAL CHEMISTRY,2018,399(8):903-910.
APA Lin, Yusheng,Cai, Xiaolian,Wang, Guiping,Ouyang, Gang,&Cao, Hong.(2018).Model construction of Niemann-Pick type C disease in zebrafish.BIOLOGICAL CHEMISTRY,399(8),903-910.
MLA Lin, Yusheng,et al."Model construction of Niemann-Pick type C disease in zebrafish".BIOLOGICAL CHEMISTRY 399.8(2018):903-910.
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