First Author | Premsrirut PK | Year | 2011 |
Journal | Cell | Volume | 145 |
Issue | 1 | Pages | 145-58 |
PubMed ID | 21458673 | Mgi Jnum | J:171191 |
Mgi Id | MGI:4948980 | Doi | 10.1016/j.cell.2011.03.012 |
Citation | Premsrirut PK, et al. (2011) A rapid and scalable system for studying gene function in mice using conditional RNA interference. Cell 145(1):145-58 |
abstractText | RNA interference is a powerful tool for studying gene function, however, the reproducible generation of RNAi transgenic mice remains a significant limitation. By combining optimized fluorescence-coupled miR30-based shRNAs with high efficiency ES cell targeting, we developed a fast, scalable pipeline for the production of shRNA transgenic mice. Using this system, we generated eight tet-regulated shRNA transgenic lines targeting Firefly and Renilla luciferases, Oct4 and tumor suppressors p53, p16(INK4a), p19(ARF) and APC and demonstrate potent gene silencing and GFP-tracked knockdown in a broad range of tissues in vivo. Further, using an shRNA targeting APC, we illustrate how this approach can identify predicted phenotypes and also unknown functions for a well-studied gene. In addition, through regulated gene silencing we validate APC/Wnt and p19(ARF) as potential therapeutic targets in T cell acute lymphoblastic leukemia/lymphoma and lung adenocarcinoma, respectively. This system provides a cost-effective and scalable platform for the production of RNAi transgenic mice targeting any mammalian gene. PAPERCLIP: |