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- W4361018266 abstract "Abstract Spinal and bulbar muscular atrophy (SBMA) is an X-linked disorder that affects males who inherit the androgen receptor ( AR ) gene with an abnormal CAG triplet repeat expansion. The resulting protein contains an elongated polyglutamine (polyQ) tract and causes motor neuron degeneration in an androgen-dependent manner. The precise molecular sequelae of SBMA are unclear. To assist with its investigation and the identification of therapeutic options, we report here a new model of SBMA in Drosophila melanogaster . We generated transgenic flies that express the full-length, human AR with a wild-type or pathogenic polyQ repeat. Each transgene is inserted into the same “safe harbor” site on the third chromosome of the fly as a single copy and in the same orientation. Expression of pathogenic AR, but not of its wild-type variant, in neurons or muscles leads to consistent, progressive defects in longevity and motility that are concomitant with polyQ-expanded AR protein aggregation and reduced complexity in neuromuscular junctions. Additional assays show adult fly eye abnormalities associated with the pathogenic AR species. The detrimental effects of pathogenic AR are accentuated by feeding flies the androgen, dihydrotestosterone. This new, robust SBMA model can be a valuable tool towards future investigations of this incurable disease." @default.
- W4361018266 created "2023-03-30" @default.
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- W4361018266 date "2023-03-27" @default.
- W4361018266 modified "2023-10-16" @default.
- W4361018266 title "A phenotypically robust model of Spinal and Bulbar Muscular Atrophy in<i>Drosophila</i>" @default.
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- W4361018266 doi "https://doi.org/10.1101/2023.03.25.534140" @default.
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