Comparative toxicity of polyglutamine, polyalanine and polyleucine tracts in Drosophila models of expanded repeat disease

Clare L van Eyk, Catherine J McLeod, Louise V O'Keefe, Robert I Richards

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)

Abstract

Homopolymeric amino acid repeat sequences in proteins are of particular interest due to the discovery that expanded copy numbers of these repeats are the molecular basis for a growing list of human genetic diseases. Repeat copy numbers above a typical normal range of polyglutamine repeats have been found to be the principal pathogenic agents in a number of these diseases, including Huntington's disease. There is emerging evidence that expansions of amino acids encoded by other reading frames of CAG/CUG repeats, including polyalanine and polyleucine, could contribute to toxicity in the 'polyglutamine' diseases. We have therefore used the Drosophila model system to investigate effects of ectopic expression of polyglutamine, polyleucine and polyalanine repeats in vivo to assess their relative toxicities and the common and distinct characteristics of the pathogenesis that they cause. We find that these homopolymeric sequences all exhibit toxicity and are able to form aggregates in Drosophila, although there are marked differences in the degree of toxicity dependent upon the tissue in which they are expressed.

Original languageEnglish
Pages (from-to)536-47
Number of pages12
JournalHuman Molecular Genetics
Volume21
Issue number3
DOIs
Publication statusPublished or Issued - 1 Feb 2012
Externally publishedYes

Keywords

  • Animals
  • Animals, Genetically Modified
  • Brain Chemistry
  • Drosophila
  • Eye
  • Male
  • Models, Animal
  • Nervous System Diseases
  • Neurons
  • Peptides
  • Repetitive Sequences, Amino Acid
  • Trinucleotide Repeat Expansion
  • Journal Article
  • Research Support, Non-U.S. Gov't

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