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Related Concept Videos

siRNA - Small Interfering RNAs02:30

siRNA - Small Interfering RNAs

Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the ATP-dependent...
Experimental RNAi02:15

Experimental RNAi

RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...

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Related Experiment Video

Updated: Jul 12, 2026

Intracerebroventricular Viral Injection of the Neonatal Mouse Brain for Persistent and Widespread Neuronal Transduction
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Local gene knockdown in the brain using viral-mediated RNA interference.

Jonathan D Hommel1, Robert M Sears, Dan Georgescu

  • 1Department of Psychiatry, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd., Dallas, Texas 75390-9070, USA.

Nature Medicine
|November 25, 2003
PubMed
Summary

Researchers developed a new viral RNA interference (RNAi) method to precisely reduce tyrosine hydroxylase (Th) gene expression in adult mouse brains. This technique rapidly created a genetic disease model exhibiting motor deficits and altered psychostimulant responses.

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Area of Science:

  • Neuroscience
  • Genetics
  • Molecular Biology

Background:

  • Conditional mutant techniques enable precise genetic modifications in mice for studying gene function in adult tissues.
  • Existing methods for conditional genetic manipulation often lack efficiency and sufficient spatial control.
  • Targeting gene function in specific neuronal populations is crucial for understanding neurological disorders.

Purpose of the Study:

  • To develop a more efficient and spatially controlled method for gene knockdown in adult mouse neurons.
  • To investigate the role of tyrosine hydroxylase (Th) in dopamine synthesis and its impact on behavior.
  • To establish a rapid and effective strategy for generating genetic disease models using viral-mediated RNA interference (RNAi).

Main Methods:

  • Utilized viral-mediated RNA interference (RNAi) to achieve targeted gene knockdown.
  • Specifically targeted the Th gene, which encodes the dopamine synthesis enzyme tyrosine hydroxylase.
  • Administered the RNAi construct to midbrain neurons in adult mice.

Main Results:

  • Successfully achieved a specific knockdown of Th gene expression within midbrain neurons.
  • Observed significant behavioral changes in the modified mice, including motor performance deficits.
  • Demonstrated a reduced response to psychostimulant administration in the Th knockdown model.

Conclusions:

  • Viral-mediated RNAi offers a powerful tool for the rapid generation and testing of genetic disease models.
  • This technique provides enhanced spatial and temporal control over gene expression in adult animals.
  • The findings suggest potential applications for RNAi in other model species and possibly in human gene therapy.