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(American Journal of Pathology. 2004;165:1535-1541.)
© 2004 American Society for Investigative Pathology

Using siRNA Technique to Generate Transgenic Animals with Spatiotemporal and Conditional Gene Knockdown

Hung-Shu Chang*, Ching-Hui Lin*, Yu-Chi Chen{dagger} and Winston C.Y. Yu*

From the National Health Research Institutes,* Taipei; and the Department of Animal Science,{dagger} National Taiwan University, Taipei, Taiwan, R.O.C.

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.




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