PUBLICATION
Model construction of Niemann-Pick Type C disease in zebrafish
- Authors
- Lin, Y., Caia, X., Wang, G., Ouyang, G., Cao, H.
- ID
- ZDB-PUB-180614-18
- Date
- 2018
- Source
- Biological chemistry 399(8): 903-910 (Journal)
- Registered Authors
- Cao, Hong, Lin, Yu-sheng, Ouyang, Gang, Wang, Gui-Ping
- Keywords
- CRISPR/Cas9, NPC1, cholesterol, zebrafish
- MeSH Terms
-
- Animals
- Body Size
- Disease Models, Animal*
- Lipid Metabolism
- Liver/chemistry
- Liver/metabolism
- Motor Activity
- Niemann-Pick Disease, Type C*/genetics
- Niemann-Pick Disease, Type C*/metabolism
- Zebrafish*/genetics
- Zebrafish*/metabolism
- PubMed
- 29897878 Full text @ Biol. Chem.
Citation
Lin, Y., Caia, X., Wang, G., Ouyang, G., Cao, H. (2018) Model construction of Niemann-Pick Type C disease in zebrafish. Biological chemistry. 399(8):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, 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 wild type and died before reaching eight 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping