关键词: 转基因果蝇, APP基因, BACE基因, DPsn基因, 阿尔茨海默症

Abstract: Alzheimer′s disease (AD) is a kind of cognitive dysfunction disease and β-amyloid (Aβ) generation is crucial for AD pathogenesis and plays a key role in disease progression. A transgenic fly expressing two copies of APP/BACE/DPsn to mimic the pathologic changes of AD might be useful for AD therapeutic drug screening. Using the classic Gal4/UAS system, we constructed the stable transgenic flies expressing two copies of APP/BACE/DPsn genes by consecutive crosses and homologus recombination. Further tests revealed that the lifespan and the medium survival time of flies expressing two copies of APP/BACE/DPsn genes were 52 d and 39 d, respectively, which were much shorter than the lifespan of 69 d and the medium survival time of 49 d of the control flies. Furthermore, the eclosion time of the flies expressing two copies of APP/BACE/DPsn genes was 3 d longer than that of the control flies, and the eclosion rate was 5.2% which was much less than the theoretical value 1∶9 (11%). The results suggest that the elav-Gal driven neuronal expression of two copies of APP/BACE/DPsn genes in flies leads to shorter lifespan and decreases viability of the offspring. These phenotypes of the transgenic fly might be used as a preliminary drug screen model for AD therapy.

Key words: Transgenic Drosophila, APP; BACE; DPsn, Alzheimer′s disease