Complete RNAi rescue of neuronal degeneration in a constitutively active Drosophila TRP channel mutant

Biochim Biophys Acta. 2004 Sep 6;1674(1):91-7. doi: 10.1016/j.bbagen.2004.06.002.

Abstract

RNA interference has been widely used to reduce the quantity of the proteins encoded by the targeted genes. A constitutively active, dominant allele of trp, TrpP365, causes massive degeneration of photoreceptors through a persistent and excessive Ca2+ influx. Here we show that a substantial reduction of the TRP channel protein by RNAi in TrpP365 heterozygotes completely rescues the neuronal degeneration and significantly improves the light-elicited responses of the eye. The reduction need not be complete, suggesting that rescue of degeneration may be possible with minimal side effects arising from overdepletion of the target protein.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium / metabolism
  • Calcium Channels / genetics
  • Calcium Channels / metabolism*
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / physiology*
  • Electroretinography
  • Humans
  • Mutation
  • Neurons / metabolism*
  • Neurons / pathology*
  • Photoreceptor Cells, Invertebrate / cytology
  • Photoreceptor Cells, Invertebrate / metabolism
  • RNA Interference*
  • TRPC Cation Channels
  • Transgenes

Substances

  • Calcium Channels
  • TRPC Cation Channels
  • Calcium