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Using siRNA technique to generate transgenic animals with spatiotemporal and conditional gene knockdown.

Based on the RNAi technique, we have developed a new approach that generates transgenic animals capable of mimicking human genetic diseases. The new system is a combination of siRNA with Cre-loxP and tetracycline-on. It has the characteristics of being stable, inheritable, and inducible, with the siRNA able to be transcribed tissue specifically. To support the ability of this new method to generate a model for a disease, we created an ABCA1-deficient mouse line that mimics Tangier disease under controlled conditions. Thus, it should now be possible to rapidly establish human genetic diseases as a whole animal model without the use of embryonic stem cell and gene targeting. This system also provides a tool for pathological and pharmacological studies of aspects peculiar to particular human genetic diseases.

Pubmed ID: 15509524


  • Chang HS
  • Lin CH
  • Chen YC
  • Yu WC


The American journal of pathology

Publication Data

November 28, 2004

Associated Grants


Mesh Terms

  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters
  • Animals
  • Cell Line, Tumor
  • Cholesterol
  • Disease Models, Animal
  • Doxycycline
  • Genetic Techniques
  • Genetic Vectors
  • Humans
  • Mice
  • Mice, Inbred ICR
  • Mice, Knockout
  • Mice, Transgenic
  • Models, Genetic
  • Phenotype
  • Plasmids
  • RNA Interference
  • RNA, Small Interfering
  • Tangier Disease
  • Time Factors
  • Tissue Distribution
  • Transfection