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

Animal Cells and Systems 2017년 21권 3호 p.160 ~ 168
전영재, 이수진, 신명철, 이장호, 서윤석, 황수진, 윤혜섭, 조경상,
소속 상세정보
전영재 ( Jeon Young-Jae ) - Konkuk University Department of Biological Sciences
이수진 ( Lee Soo-Jin ) - Konkuk University Department of Biological Sciences
신명철 ( Shin Myoung-Chul ) - Konkuk University Department of Biological Sciences
이장호 ( Lee Jang-Ho ) - Konkuk University Department of Biological Sciences
서윤석 ( Suh Yoon-Seok ) - Konkuk University Department of Biological Sciences
황수진 ( Hwang Soo-Jin ) - Konkuk University Department of Biological Sciences
윤혜섭 ( Yun Hye-Sup ) - Konkuk University Department of Biological Sciences
조경상 ( Cho Kyoung-Sang ) - Konkuk University Department of Biological Sciences

Abstract


Drosophila melanogaster expressing amyloid-β42 (Aβ42) transgenes have been used as models to study Alzheimer’s disease. Various Aβ42 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 Aβ42 transgenic lines, UAS-Aβ422X, UAS-Aβ42BL33770, UAS-Aβ4211C39, and UAS-Aβ42H29.3. Among the four transgenic lines, only UAS-Aβ422X has two copies of the upstream activation sequence-amyloid-β42 (UAS-Aβ42) transgene, while remaining three have one copy. UAS-Aβ42BL33770 has the 3′ untranslated region of Drosophila α-tubulin, while the others have that of SV40. UAS-Aβ4211C39 and UAS-Aβ42H29.3 have the rat pre-proenkephalin signal peptide, while UAS-Aβ422X and UAS-Aβ42BL33770 have that of the fly argos protein. When the transgenes were expressed ectopically in the developing eyes of the flies, UAS-Aβ422X transgene resulted in a strongly reduced and rough eye phenotype, while UAS-Aβ42BL33770 only showed a strong rough eye phenotype; UAS-Aβ42H29.3 and UAS-Aβ4211C39 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-Aβ422X, followed by UAS-Aβ42BL33770, UAS-Aβ4211C39, and UAS-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 expressed UAS-Aβ4211C39 or UAS-Aβ42H29.3 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.

키워드

Alzheimer’s disease; amyloid-β42; Drosophila; UAS-Aβ42

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