Cellular and Molecular Neurobiology

, Volume 24, Issue 1, pp 109–122

Expression of Expanded Polyglutamine Protein Induces Behavioral Changes in Drosophila (Polyglutamine-Induced Changes in Drosophila)

Authors

  • Yun-Taik Kim
    • Department of Life ScienceSogang University
  • Sang Min Shin
    • Department of Life ScienceSogang University
    • Clinical Research CenterSamsung Biomedical Research Institute
  • Won Yong Lee
    • Department of NeurologySungkyunkwan University, School of Medicine, Samsung Medical Center
  • Gyeong-Moon Kim
    • Department of NeurologySungkyunkwan University, School of Medicine, Samsung Medical Center
  • Dong Kyu Jin
    • Department of PediatricsSungkyunkwan University, School of Medicine, Samsung Medical Center
Article

DOI: 10.1023/B:CEMN.0000012716.14075.25

Cite this article as:
Kim, Y., Shin, S.M., Lee, W.Y. et al. Cell Mol Neurobiol (2004) 24: 109. doi:10.1023/B:CEMN.0000012716.14075.25

Abstract

Spinocerebellar ataxia type-3 or Machado–Joseph disease (SCA3/MJD) is an autosomal dominant neurodegenerative disease caused by triplet nucleotide expansion. The expansion of the polyglutamine tract near the C terminus of the MJD1 gene product, ataxin-3, above a threshold of 40 glutamine repeats causes neuronal loss and degeneration. The expanded ataxin-3 forms aggregates, and nuclear inclusions, within neurons, possibly due to the misfolding of mutant proteins. Here we report upon the behavioral test changes related to truncated and expanded forms of MJD protein (MJDtr) in Drosophila, and show that expanded MJDtr, when expressed in the nervous system, causes characteristic locomotor dysfunction and anosmia. This phenomenon has not been previously reported in humans or in transgenic Drosophila models. In addition, the in vivo expression of the antiapoptotic gene bcl-2 showed no evidence of ameliorating the deleterious effect of MJDtr-Q78s, either in the eye or in the nervous system. The study shows that such Drosophila transgenic models express olfactory dysfunction and ataxic behavior as observed in human patients.

polyglutamineMachado–Joseph disease (MJD)spinocerebellar ataxia 3 (SCA3)Drosophilabehavioral dysfunctionbcl-2

Copyright information

© Plenum Publishing Corporation 2004