Model construction of Niemann-Pick type C disease in zebrafish | |
Lin, Yusheng; Cai, Xiaolian; Wang, Guiping; Ouyang, Gang; Cao, Hong![]() | |
2018-08-01 | |
Source Publication | BIOLOGICAL CHEMISTRY
![]() |
ISSN | 1431-6730 |
Volume | 399Issue: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. |
Keyword | cholesterol CRISPR/Cas9 NPC1 zebrafish |
DOI | 10.1515/hsz-2018-0118 |
Funding Organization | 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 ; State Key Laboratory of Freshwater Ecology and Biotechnology |
Indexed By | SCI |
Language | 英语 |
Funding Project | State Key Laboratory of Freshwater Ecology and Biotechnology[2012FB04] |
WOS Research Area | Biochemistry & Molecular Biology |
WOS Subject | Biochemistry & Molecular Biology |
WOS ID | WOS:000438949700009 |
WOS Keyword | STEROL-SENSING DOMAIN ; TRANSGENIC ZEBRAFISH ; NPC1 PROTEIN ; IDENTIFICATION ; MUTATIONS ; CHOLESTEROL ; NEURODEGENERATION ; HOMEOSTASIS ; PHENOTYPE ; NEURONS |
Publisher | WALTER DE GRUYTER GMBH |
Funding Organization | 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 ; State Key Laboratory of Freshwater Ecology and Biotechnology |
Citation statistics | |
Document Type | 期刊论文 |
Identifier | http://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 Author | Cao, Hong |
Affiliation | Chinese 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. |
Files in This Item: | ||||||
File Name/Size | DocType | Version | Access | License | ||
[Biological Chemistr(773KB) | 期刊论文 | 作者接受稿 | 开放获取 | CC BY-NC-SA | View Application Full Text |
Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.
Edit Comment