TY - JOUR
T1 - Tissue-specific and reversible RNA interference in transgenic mice
AU - Dickins, Ross Alexander
AU - McJunkin, Katherine
AU - Hernando-Monge, Eva M
AU - Premsrirut, Prem K
AU - Krizhanovsky, Valery
AU - Burgess, Darren J
AU - Kim, Sang Yong
AU - Cordon-Cardo, Carlos
AU - Zender, Lars
AU - Hannon, Gregory J
AU - Lowe, Scott William
PY - 2007
Y1 - 2007
N2 - 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.
AB - 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.
UR - http://www.nature.com.ezproxy.lib.monash.edu.au/ng/journal/v39/n7/full/ng2045.html
U2 - 10.1038/ng2045
DO - 10.1038/ng2045
M3 - Article
SN - 1061-4036
VL - 39
SP - 914
EP - 921
JO - Nature Genetics
JF - Nature Genetics
ER -