Local knockdown of genes in the brain using small interfering RNA: a phenotypic comparison with knockout animals.


Journal Article

BACKGROUND: Recent reports have suggested effectiveness of RNA interference (RNAi) for the analysis of gene functions in the brain. This study sought to determine the efficiency of local small interfering RNA (siRNA) injections, comparing this approach with animals generated through classical gene targeting. METHODS: Small interfering RNA against dopamine transporter (DAT) (35 microg/14 days) or tyrosine hydroxylase (TH) (15 microg/3 days) was injected into the ventral tegmental/substantia nigra areas of the brain of adult wildtype or DAT-knockout mice, respectively. RESULTS: Local injections of siRNA resulted in a 35% to 40% reduction of DAT and TH protein levels in the striatum, respectively. Despite negligible effect of DAT knockdown on novelty-induced locomotion, the locomotor response of DAT siRNA treated animals to amphetamine was blunted similar to what is observed in the DAT heterozygote animals. Since incomplete reduction of TH levels in normal mice does not produce behavioral effects, TH siRNA experiments were carried out in DAT-knockout animals that show increased dependence on newly synthesized dopamine. Knockdown of TH in these animals resulted in reduced basal locomotion. CONCLUSIONS: Local injection of siRNA in the brain reduced gene expression by 40% to 50%, suggesting that siRNA-mediated knockdown of genes in the brain can be a complementary tool to classical transgenesis for the analysis of gene functions.

Full Text

Duke Authors

Cited Authors

  • Salahpour, A; Medvedev, IO; Beaulieu, J-M; Gainetdinov, RR; Caron, MG

Published Date

  • January 1, 2007

Published In

Volume / Issue

  • 61 / 1

Start / End Page

  • 65 - 69

PubMed ID

  • 16712807

Pubmed Central ID

  • 16712807

International Standard Serial Number (ISSN)

  • 0006-3223

Digital Object Identifier (DOI)

  • 10.1016/j.biopsych.2006.03.020


  • eng

Conference Location

  • United States