KMID : 1161520170210030160
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Animal Cells and Systems 2017 Volume.21 No. 3 p.160 ~ p.168
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Phenotypic differences between Drosophila Alzheimer¡¯s disease models expressing human A¥â42 in the developing eye and brain
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Jeon Young-Jae
Lee Soo-Jin Shin Myoung-Chul Lee Jang-Ho Suh Yoon-Seok Hwang Soo-Jin Yun Hye-Sup Cho Kyoung-Sang
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Abstract
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Drosophila melanogaster expressing amyloid-¥â42 (A¥â42) transgenes have been used as models to study Alzheimer¡¯s disease. Various A¥â42 transgenes 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 used A¥â42 transgenic lines, UAS-A¥â422X, UAS-A¥â42BL33770, UAS-A¥â4211C39, and UAS-A¥â42H29.3. Among the four transgenic lines, only UAS-A¥â422X has two copies of the upstream activation sequence-amyloid-¥â42 (UAS-A¥â42) transgene, while remaining three have one copy. UAS-A¥â42BL33770 has the 3¡Ç untranslated region of Drosophila ¥á-tubulin, while the others have that of SV40. UAS-A¥â4211C39 and UAS-A¥â42H29.3 have the rat pre-proenkephalin signal peptide, while UAS-A¥â422X and UAS-A¥â42BL33770 have that of the fly argos protein. When the transgenes were expressed ectopically in the developing eyes of the flies, UAS-A¥â422X transgene resulted in a strongly reduced and rough eye phenotype, while UAS-A¥â42BL33770 only showed a strong rough eye phenotype; UAS-A¥â42H29.3 and UAS-A¥â4211C39 had mild rough eyes. The levels of cell death and reactive oxygen species (ROS) in the eye imaginal discs were consistently the highest in UAS-A¥â422X, followed by UAS-A¥â42BL33770, UAS-A¥â4211C39, and UAS-A¥â42H29.3. Surprisingly, the reduction in survival during the development of these lines did not correlate with cell death or ROS levels. The flies which expressed UAS-A¥â4211C39 or UAS-A¥â42H29.3 experienced greatly reduced survival rates, although low levels of ROS or cell death were detected. Collectively, our results demonstrated that different Drosophila AD models show different phenotypic severity, and suggested that different transgenes may have different modes of cytotoxicity.
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KEYWORD
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Alzheimer¡¯s disease, amyloid-¥â42, Drosophila, UAS-A¥â42
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