Non-coding RNA as a trigger of neuropathologic disorder phenotypes in transgenic Drosophila

J Neural Transm (Vienna). 2008 Dec;115(12):1629-42. doi: 10.1007/s00702-008-0078-8. Epub 2008 Sep 9.

Abstract

At most, many protein-misfolding diseases develop as environmentally induced sporadic disorders. Recent studies indicate that the dynamic interplay between a wide repertoire of noncoding RNAs and the environment play an important role in brain development and pathogenesis of brain disorders. To elucidate this new issue, novel animal models which reproduce the most prominent disease manifestations are required. For this, transgenic Drosophila strains were constructed to express small highly structured, non-coding RNA under control of a heat shock promoter. Expression of the RNA induced formation of intracellular aggregates revealed by Thioflafin T in embryonic cell culture and Congo Red in the brain of transgenic flies. Also, this strongly perturbed the brain control of locomotion monitored by the parameters of sound production and memory retention of young 5-day-old males. This novel model demonstrates that expression of non-coding RNA alone is sufficient to trigger neuropathology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Base Sequence / genetics
  • Brain / abnormalities
  • Brain / metabolism
  • Brain / pathology
  • Cells, Cultured
  • Cognition Disorders / genetics*
  • Cognition Disorders / pathology
  • Cognition Disorders / physiopathology
  • Disease Models, Animal
  • Drosophila Proteins / biosynthesis
  • Drosophila Proteins / genetics
  • Drosophila melanogaster / genetics*
  • Gene Expression Regulation, Developmental / genetics
  • Genetic Predisposition to Disease / genetics*
  • Inclusion Bodies / metabolism
  • Inclusion Bodies / pathology
  • Male
  • Memory Disorders / genetics
  • Memory Disorders / pathology
  • Memory Disorders / physiopathology
  • Molecular Sequence Data
  • Movement Disorders / genetics*
  • Movement Disorders / pathology
  • Movement Disorders / physiopathology
  • Nervous System Malformations / genetics*
  • Nervous System Malformations / pathology
  • Nervous System Malformations / physiopathology
  • Phenotype
  • Protein Folding
  • RNA, Untranslated / genetics*

Substances

  • Drosophila Proteins
  • RNA, Untranslated