A zebrafish melanophore model of amyloid beta toxicity.
Reliable animal models are required to facilitate the understanding of neurodegenerative pathways in Alzheimer's disease. Animal models can also be employed to search for disease-modifying drugs. The embryos and larvae of zebrafish are particularly advantageous for this purpose. For Alzheimer's disease, drugs that can ameliorate amyloid beta (A beta) toxicity have therapeutic and/or prophylactic potential. We attempted to generate a zebrafish model of A beta toxicity that would be viable and fertile but have a highly visible pigmentation phenotype in larvae. The larvae could then be arrayed in microtiter plates to screen compound libraries for drugs acting to reduce A beta toxicity. We used the promoter of the zebrafish mitfa (nacre) gene to drive expression of the pathological 42 amino acid species of human A beta, A beta(42), specifically in the highly visible melanophores (melanocytes) of transgenic zebrafish. However, the transgenic fish only showed an aberrant pigment phenotype in adults at the advanced age of 16 months. Nevertheless, our results show that alteration of zebrafish pigment pattern may be useful for analysis of toxic peptide action.
Newman
Morgan
M
Discipline of Genetics, School of Molecular and Biomedical Science, The University of Adelaide, Adelaide, Australia. morgan.newman@adelaide.edu.au
Wilson
Lachlan
L
Camp
Esther
E
Verdile
Giuseppe
G
Martins
Ralph
R
Lardelli
Michael
M
D000544:Alzheimer Disease / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D017931:DNA Primers / Q000235:genetics; D004195:Disease Models, Animal; D055808:Drug Discovery / Q000379:methods; D018014:Gene Transfer Techniques; D017403:In Situ Hybridization; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics / Q000378:metabolism; D010858:Pigmentation / Q000187:drug effects / Q000502:physiology; D016133:Polymerase Chain Reaction; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
D016229:Amyloid beta-Peptides; D017931:DNA Primers; D051739:Microphthalmia-Associated Transcription Factor; D029961:Zebrafish Proteins; C497237:mitfa protein, zebrafish