PUBLICATION
Generation of Alzheimer's Disease Transgenic Zebrafish Expressing Human APP Mutation under Control of Zebrafish appb Promotor
- Authors
- Pu, Y.Z., Liang, L., Fu, A.L., Liu, Y., Sun, L., Li, Q., Wu, D., Sun, M.J., Zhang, Y.G., Zhao, B.Q.
- ID
- ZDB-PUB-161217-13
- Date
- 2017
- Source
- Current Alzheimer research 14(6): 668-679 (Journal)
- Registered Authors
- Liu, Yan, Zhao, Baoquan
- Keywords
- Alzheimer's disease transgenic model, human APP Swedish mutation, Zebrafish appb promoter, Aβ deposition, microvascular abnormalities, neuron loss
- MeSH Terms
-
- Alzheimer Disease/complications
- Alzheimer Disease/genetics*
- Alzheimer Disease/pathology
- Amyloid beta-Peptides/metabolism
- Amyloid beta-Protein Precursor/genetics*
- Amyloidosis/etiology
- Animals
- Animals, Genetically Modified
- Brain/metabolism
- Brain/pathology
- Brain/ultrastructure
- Cerebral Amyloid Angiopathy/etiology*
- Cerebral Amyloid Angiopathy/genetics
- Disease Models, Animal
- Exploratory Behavior/physiology
- Gene Expression Regulation/genetics*
- Green Fluorescent Proteins/genetics
- Green Fluorescent Proteins/metabolism
- Humans
- Maze Learning/physiology
- Microscopy, Electron, Transmission
- Microvessels/metabolism
- Microvessels/pathology
- Microvessels/ultrastructure
- Mutation/genetics*
- Promoter Regions, Genetic/physiology*
- RNA, Messenger/metabolism
- Zebrafish
- PubMed
- 27978793 Full text @ Curr Alzheimer Res
Citation
Pu, Y.Z., Liang, L., Fu, A.L., Liu, Y., Sun, L., Li, Q., Wu, D., Sun, M.J., Zhang, Y.G., Zhao, B.Q. (2017) Generation of Alzheimer's Disease Transgenic Zebrafish Expressing Human APP Mutation under Control of Zebrafish appb Promotor. Current Alzheimer research. 14(6):668-679.
Abstract
Amyloid peptide precursor (APP) as the precursor protein of peptide beta-amyloid (β-amyloid, Aβ), which is thought to play a central role in the pathogenesis of Alzheimer's disease (AD), also has an important effect on the development and progression of AD. Through knocking-in APP gene in animals, numerous transgenic AD models have been set up for the investigation of the mechanisms behind AD pathogenesis and the screening of anti-AD drugs. However, there are some limitations to these models and here is a need for such an AD model that is economic as well as has satisfactory genetic homology with human. Here, a new AD transgenic model was successfully generated by knocking a mutant human APP gene (APPsw) in zebrafish with appb promoter of zebrafish to drive the expression of APPsw, Behavioral observation demonstrated that the transgenic zebrafish had AD-like symptoms. Fluorescent image and immunochemistry stain showed and RT-PCR and western blot assay confirmed that APPsw was successfully expressed in the brain, heart, eyes and vasculature of the transgenic zebrafish. Histopathological observation found that there were cerebral β amyloidosis and angiopathy (CAA), well simulating the pathological characters of AD. These results suggest that APPsw transgenic zebrafish can be used as an economic AD transgenic model with high genetic homology with human.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping