Tissue-specific and reversible RNA interference in transgenic mice Journal Article
| Authors: | Dickins, R. A.; McJunkin, K.; Hernando, E.; Premsrirut, P. K.; Krizhanovsky, V.; Burgess, D. J.; Kim, S. Y.; Cordon-Cardo, C.; Zender, L.; Hannon, G. J.; Lowe, S. W. |
| Article Title: | Tissue-specific and reversible RNA interference in transgenic mice |
| Abstract: | Genetically engineered mice provide powerful tools for understanding mammalian gene function. These models traditionally rely on gene overexpression from transgenes or targeted, irreversible gene mutation. By adapting the tetracycline (tet)-responsive system previously used for gene overexpression, we have developed a simple transgenic system to reversibly control endogenous gene expression using RNA interference (RNAi) in mice. Transgenic mice harboring a tet-responsive RNA polymerase II promoter driving a microRNA-based short hairpin RNA targeting the tumor suppressor Trp53 reversibly express short hairpin RNA when crossed with existing mouse strains expressing general or tissue-specific 'tet-on' or 'tet-off' transactivators. Reversible Trp53 knockdown can be achieved in several tissues, and restoring Trp53 expression in lymphomas whose development is promoted by Trp53 knockdown leads to tumor regression. By leaving the target gene unaltered, this approach permits tissue-specific, reversible regulation of endogenous gene expression in vivo, with potential broad application in basic biology and drug target validation. © 2007 Nature Publishing Group. |
| Keywords: | controlled study; protein expression; gene mutation; promoter region; nonhuman; animal cell; mouse; mammalia; animals; mice; animal tissue; gene targeting; mus; microrna; gene expression; animal experiment; animal model; small interfering rna; gene function; rna interference; tumor regression; protein p53; transgenic mouse; mus musculus; mice, transgenic; drug delivery systems; genetic engineering; lymphoma; organ specificity; transactivation; transgene; tumor suppressor protein; tetracycline; rna polymerase ii; tissue specificity; genetic regulation; promoter regions (genetics) |
| Journal Title: | Nature Genetics |
| Volume: | 39 |
| Issue: | 7 |
| ISSN: | 1061-4036 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2007-07-01 |
| Start Page: | 914 |
| End Page: | 921 |
| Language: | English |
| DOI: | 10.1038/ng2045 |
| PUBMED: | 17572676 |
| PROVIDER: | scopus |
| PMCID: | PMC4595852 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 59" - "Export Date: 17 November 2011" - "CODEN: NGENE" - "Source: Scopus" |
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
-
22Hernando -
612
Cordon-Cardo
Related MSK Work