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A rapid and scalable system for studying gene function in mice using conditional RNA interference.

Cell | Apr 1, 2011

http://www.ncbi.nlm.nih.gov/pubmed/21458673

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:

Pubmed ID: 21458673 RIS Download

Mesh terms: Adenocarcinoma | Animals | Embryonic Stem Cells | Gene Knockdown Techniques | Lung Neoplasms | Mice | Mice, Transgenic | MicroRNAs | Precursor T-Cell Lymphoblastic Leukemia-Lymphoma | RNA Interference | RNA Processing, Post-Transcriptional | RNA, Small Interfering | Signal Transduction | Wnt Proteins

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Associated grants

  • Agency: NCI NIH HHS, Id: P01 CA013106
  • Agency: NCI NIH HHS, Id: P01 CA013106-40
  • Agency: NCI NIH HHS, Id: P30 CA008748
  • Agency: NIGMS NIH HHS, Id: R01 GM062534
  • Agency: Howard Hughes Medical Institute, Id:
  • Agency: Howard Hughes Medical Institute, Id:

Mouse Genome Informatics (Data, Gene Annotation)

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