Establishment of APPswe/PS1 dE9/TAU triple transgenic rat model of alzheimer disease
10.3969/j.issn.1671.7856.2014.003.013
- VernacularTitle:APPswe／PS1 dE9／TAU 三转基因阿尔兹海默病大鼠模型的建立
- Author:
Li ZHANG
;
Wei CHEN
;
Xu ZHANG
;
Caixian SUN
;
Lianfeng ZHANG
- Publication Type:Journal Article
- Keywords:
Transgenic;
Microtubule-associated protein tau;
Alzheimer’ s disease;
Neurofibrillary tangles;
Rat
- From:
Chinese Journal of Comparative Medicine
2014;(3):61-65,66
- CountryChina
- Language:Chinese
-
Abstract:
Objective To develop a model that could roundly show the phenotypes of human alzheimer disease (AD), the triple-transgenic rat model harboring APP(Swe), PS1dE9, and TAU transgenes was established in view of the advantage of rat as an important animal model on the research of nerve system .Methods APPswe/PS1dE9/TAU triple transgenic rat AD rats were generated on a SD background by co-injecting rat pronuclei with two human genes driven by the mouse prion promoter:‘Swedish’ mutant human APP (APPsw) and exon 9 mutant human presenilin-1 (PS1dE9) and human microtubule-associated protein tau gene under the control of PDGF promoter .Transgene integration was confirmed by genotyping and expression levels were evaluated by western blot ( WB ) of brain homogenates .The pathological changes were detected by human Abeta, TAU and Phospho-PHF-TAU immunohistochemistry staining (IHC).The behavioral and cognitive changes were evaluated by Morris water maze .Results One transgenic rat lines with high human APP ( Swe ) , PS1dE9, and TAU transgenic expression was selected from three transgenic founders .Compared with the wild type rat , the transgenic rat showed significant learning and memory impairments in the Morris water maze at 6 months of age .The triple transgenic rat manifested hyperphosphorylated tau and obvious aggregation of amyloid -β( Aβ) in the brain cortex and hippocampus.Conclusion APPswe/PS1dE9/TAU triple transgenic rat AD model was established .The triple transgenic AD rat fills a critical need for a next-generation animal model to enable basic and translational AD research .
