Discipline of Genetics, School of Molecular and Biomedical Science, The University of Adelaide, Adelaide, Australia.
Zebrafish. 2010 Jun;7(2):155-9. doi: 10.1089/zeb.2009.0628.
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.
需要可靠的动物模型来促进对阿尔茨海默病神经退行性途径的理解。动物模型也可用于寻找疾病修饰药物。斑马鱼的胚胎和幼虫在这方面特别有优势。对于阿尔茨海默病，能够改善淀粉样蛋白 β（Aβ）毒性的药物具有治疗和/或预防潜力。我们试图生成一种可行且有生育能力的斑马鱼 Aβ毒性模型，但在幼虫中具有高度可见的色素沉着表型。然后可以将幼虫排列在微量滴定板中，筛选可减少 Aβ毒性的化合物库中的药物。我们使用斑马鱼 mitfa（珍珠）基因的启动子来驱动人类 Aβ的病理 42 个氨基酸种 Aβ（42）的表达，该基因特异性地在转基因斑马鱼的高度可见黑素细胞（黑素细胞）中表达。然而，转基因鱼仅在 16 个月的高龄时在成年期表现出异常的色素沉着表型。尽管如此，我们的结果表明，斑马鱼色素模式的改变可能有助于分析有毒肽的作用。
