title: Generation of Alzheimer's Disease Transgenic Zebrafish Expressing Human APP Mutation Under Control of Zebrafish appb Promotor.
abstract: Amyloid peptide precursor (APP) as the precursor protein of peptide betaamyloid (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.
  
  
  
  We generated a new AD transgenic model by knocking a mutant human APP gene (APPsw) in zebrafish with appb promoter of zebrafish to drive the expression of APPsw.
  
  
  
  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. Behavioral observation demonstrated that the transgenic zebrafish had AD-like symptoms. Histopathological observation found that there were cerebral β-amyloidosis and angiopathy (CAA), which induced neuron loss and enlarged pervascular space.
  
  
  
  These results suggest that APPsw transgenic zebrafish well simulate the pathological characters of AD and can be used as an economic AD transgenic model. Furthermore, the new model suggested that APP can express in microvasculatures and cause the Aβ generation and deposition in cerebral vessel which further destroys cerebral vascular structure resulting in the development and/or the progress of AD.
authors.affiliation: State Key Laboratory of Toxicology and Medical Countermeasures, Institute of Pharmacology and Toxicology, Academy of Military Medical Science, Beijing 100850, China.
authors.forename: Yun-Zhu
authors.initials: YZ
authors.lastname: Pu
authors.affiliation: Attached Hospital, Inner Mongolia University for Nationalities, Tongliao 028000, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Liang
authors.affiliation: College of Pharmaceutical Sciences, Southwest University, Chongqing 400716, China.
authors.forename: Ai-Ling
authors.initials: AL
authors.lastname: Fu
authors.affiliation: State Key Laboratory of Toxicology and Medical Countermeasures, Institute of Pharmacology and Toxicology, Academy of Military Medical Science, Beijing 100850, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Toxicology and Medical Countermeasures, Institute of Pharmacology and Toxicology, Academy of Military Medical Science, Beijing 100850, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Toxicology and Medical Countermeasures, Institute of Pharmacology and Toxicology, Academy of Military Medical Science, Beijing 100850, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Mechanical Engineering, Tsinghua University, Beijing 100084, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Toxicology and Medical Countermeasures, Institute of Pharmacology and Toxicology, Academy of Military Medical Science, Beijing 100850, China.
authors.forename: Man-Ji
authors.initials: MJ
authors.lastname: Sun
authors.affiliation: Institute of Pharmacology and Toxicology, Academy of Military Medical Science, No. 27 Taiping Road, Beijing 100850, China.
authors.forename: Ying-Ge
authors.initials: YG
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Toxicology and Medical Countermeasures, Institute of Pharmacology and Toxicology, Academy of Military Medical Science, Beijing 100850, China.
authors.forename: Bao-Quan
authors.initials: BQ
authors.lastname: Zhao
mesh_terms: D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000686:Amyloidosis / Q000209:etiology; D000818:Animals; D030801:Animals, Genetically Modified; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D016657:Cerebral Amyloid Angiopathy / Q000209:etiology* / Q000235:genetics; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000502:physiology; D005786:Gene Expression Regulation / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D018782:Maze Learning / Q000502:physiology; D046529:Microscopy, Electron, Transmission; D055806:Microvessels / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D009154:Mutation / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D015027:Zebrafish
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D012333:RNA, Messenger; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins
keywords: Alzheimer's disease transgenic model; Aβ deposition; Zebrafish appb promoter; human APP Swedish mutation; microvascular abnormalities; neuron loss