Phenotypic differences between Drosophila Alzheimer’s disease models expressing human Aβ42 in the developing eye and brain.

Jeon, Youngjae; Lee, Soojin; Shin, Myoungchul; Lee, Jang Ho; Suh, Yoon Seok; Hwang, Soojin; Yun, Hye Sup; Cho, Kyoung Sang

Drosophila melanogasterexpressing amyloid-β42 (Aβ42) transgenes have been used as models to study Alzheimer’s disease. VariousAβ42transgenes with different structures induce different phenotypes, which make it difficult to compare data among studies which use different transgenic lines. In this study, we compared the phenotypes of four frequently usedAβ42transgenic lines,UAS-Aβ422X,UAS-Aβ42BL33770,UAS-Aβ4211C39, andUAS-Aβ42H29.3. Among the four transgenic lines, onlyUAS-Aβ422Xhas two copies of the upstream activation sequence-amyloid-β42 (UAS-Aβ42) transgene, while remaining three have one copy.UAS-Aβ42BL33770has the 3′ untranslated region ofDrosophila α-tubulin, while the others have that of SV40.UAS-Aβ4211C39andUAS-Aβ42H29.3have the rat pre-proenkephalin signal peptide, whileUAS-Aβ422XandUAS-Aβ42BL33770have that of the fly argos protein. When the transgenes were expressed ectopically in the developing eyes of the flies,UAS-Aβ422Xtransgene resulted in a strongly reduced and rough eye phenotype, whileUAS-Aβ42BL33770only showed a strong rough eye phenotype;UAS-Aβ42H29.3andUAS-Aβ4211C39had mild rough eyes. The levels of cell death and reactive oxygen species (ROS) in the eye imaginal discs were consistently the highest inUAS-Aβ422X, followed byUAS-Aβ42BL33770,UAS-Aβ4211C39, andUAS-Aβ42H29.3. Surprisingly, the reduction in survival during the development of these lines did not correlate with cell death or ROS levels. The flies which expressedUAS-Aβ4211C39orUAS-Aβ42H29.3experienced greatly reduced survival rates, although low levels of ROS or cell death were detected. Collectively, our results demonstrated that differentDrosophilaAD models show different phenotypic severity, and suggested that different transgenes may have different modes of cytotoxicity. Abbreviations:Aβ42: amyloid-β42; AD: Alzheimer’s disease; UAS: upstream activation sequence

DROSOPHILA melanogaster; ANIMAL models of Alzheimer's disease; TRANSGENIC organisms; AMYLOID; TRANSGENES; DISEASES

Animal Cells & Systems, 2017, Vol 21, Issue 3, p160

1976-8354

Academic Journal

10.1080/19768354.2017.1313777