Expanded polyglutamine protein forms nuclear inclusions and causes neural degeneration in Drosophila

Cell. 1998 Jun 12;93(6):939-49. doi: 10.1016/s0092-8674(00)81200-3.


Spinocerebellar ataxia type 3 (SCA3/MJD) is one of at least eight human neurodegenerative diseases caused by glutamine-repeat expansion. We have recreated glutamine-repeat disease in Drosophila using a segment of the SCA3/MJD protein. Targeted expression of the protein with an expanded polyglutamine repeat led to nuclear inclusion (NI) formation and late-onset cell degeneration. Differential sensitivity to the mutant transgene was observed among different cell types, with neurons being particularly susceptible; NI formation alone was not sufficient for degeneration. The viral antiapoptotic gene P35 mitigated polyglutamine-induced degeneration in vivo. Our results demonstrate that cellular mechanisms of human glutamine-repeat disease are conserved in invertebrates. This fly model will aid in identifying additional factors that modulate neurodegeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Apoptosis
  • Ataxin-3
  • Baculoviridae
  • Cell Nucleus / pathology
  • Drosophila
  • Eye / pathology
  • Gene Targeting
  • Humans
  • Inclusion Bodies / genetics*
  • Inhibitor of Apoptosis Proteins
  • Larva
  • Machado-Joseph Disease / genetics
  • Machado-Joseph Disease / pathology*
  • Nerve Degeneration / genetics*
  • Nerve Tissue Proteins / genetics*
  • Nuclear Proteins
  • Organ Specificity
  • Peptides* / genetics
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Trinucleotide Repeats
  • Viral Proteins / genetics
  • Viral Proteins / physiology


  • Inhibitor of Apoptosis Proteins
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Peptides
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Viral Proteins
  • inhibitor of apoptosis, Nucleopolyhedrovirus
  • polyglutamine
  • ATXN3 protein, human
  • Ataxin-3