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.
Chang
Hung-Shu
HS
National Health Research Institutes, 3F, 109, Min-Chuan East Road, Sec 6, Taipei 114, Taiwan, ROC.
Lin
Ching-Hui
CH
Chen
Yu-Chi
YC
Yu
Winston C Y
WC
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000818:Animals; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000097:blood; D004195:Disease Models, Animal; D004318:Doxycycline / Q000494:pharmacology; D005821:Genetic Techniques; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008957:Models, Genetic; D010641:Phenotype; D010957:Plasmids / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism*; D013631:Tangier Disease / Q000235:genetics; D013997:Time Factors; D014018:Tissue Distribution; D014162:Transfection
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D034741:RNA, Small Interfering; D002784:Cholesterol; D004318:Doxycycline