Document Type
Article
Publication Date
12-8-2023
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 toward future investigations of this incurable disease.
Recommended Citation
Richardson, Kristin; Sengupta, Medha; Sujkowski, Alyson; Libohova, Kozeta; Harris, Autumn C.; Wessells, Robert; Merry, Diane E.; and Todi, Sokol V., "A Phenotypically Robust Model of Spinal and Bulbar Muscular Atrophy in Drosophila" (2023). Department of Biochemistry and Molecular Biology Faculty Papers. Paper 248.
https://jdc.jefferson.edu/bmpfp/248
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
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Language
English
Included in
Congenital, Hereditary, and Neonatal Diseases and Abnormalities Commons, Medical Genetics Commons
Comments
This article is the author's final published version in Journal of Neuroscience Research, Volume 102, Issue 1, 2023, Article number e25278.
The published version is available at https://doi.org/10.1002/jnr.25278. Copyright © 2023 The Authors. Journal of Neuroscience Research published by Wiley Periodicals LLC.