TY - JOUR
T1 - PiggyBac transposon mutagenesis
T2 - A tool for cancer gene discovery in mice
AU - Rad, Roland
AU - Rad, Lena
AU - Wang, Wei
AU - Cadinanos, Juan
AU - Vassiliou, George
AU - Rice, Stephen
AU - Campos, Lia S.
AU - Yusa, Kosuke
AU - Banerjee, Ruby
AU - Li, Meng Amy
AU - De La Rosa, Jorge
AU - Strong, Alexander
AU - Lu, Dong
AU - Ellis, Peter
AU - Conte, Nathalie
AU - Yang, Fang Tang
AU - Liu, Pentao
AU - Bradley, Allan
PY - 2010/11/19
Y1 - 2010/11/19
N2 - Transposons are mobile DNA segments that can disrupt gene function by inserting in or near genes. Here, we show that insertional mutagenesis by the PiggyBac transposon can be used for cancer gene discovery in mice. PiggyBac transposition in genetically engineered transposon-transposase mice induced cancers whose type (hematopoietic versus solid) and latency were dependent on the regulatory elements introduced into transposons. Analysis of 63 hematopoietic tumors revealed that PiggyBac is capable of genome-wide mutagenesis. The PiggyBac screen uncovered many cancer genes not identified in previous retroviral or Sleeping Beauty transposon screens, including Spic, which encodes a PU.1-related transcription factor, and Hdac7, a histone deacetylase gene. PiggyBac and Sleeping Beauty have different integration preferences. Tomaximize the utility of the tool, we engineered 21 mouse lines to be compatible with both transposon systems in constitutive, tissue- or temporal-specific mutagenesis. Mice with different transposon types, copy numbers, and chromosomal locations support wide applicability.
AB - Transposons are mobile DNA segments that can disrupt gene function by inserting in or near genes. Here, we show that insertional mutagenesis by the PiggyBac transposon can be used for cancer gene discovery in mice. PiggyBac transposition in genetically engineered transposon-transposase mice induced cancers whose type (hematopoietic versus solid) and latency were dependent on the regulatory elements introduced into transposons. Analysis of 63 hematopoietic tumors revealed that PiggyBac is capable of genome-wide mutagenesis. The PiggyBac screen uncovered many cancer genes not identified in previous retroviral or Sleeping Beauty transposon screens, including Spic, which encodes a PU.1-related transcription factor, and Hdac7, a histone deacetylase gene. PiggyBac and Sleeping Beauty have different integration preferences. Tomaximize the utility of the tool, we engineered 21 mouse lines to be compatible with both transposon systems in constitutive, tissue- or temporal-specific mutagenesis. Mice with different transposon types, copy numbers, and chromosomal locations support wide applicability.
UR - http://www.scopus.com/inward/record.url?scp=78449294626&partnerID=8YFLogxK
U2 - 10.1126/science.1193004
DO - 10.1126/science.1193004
M3 - Article
C2 - 20947725
AN - SCOPUS:78449294626
SN - 0036-8075
VL - 330
SP - 1104
EP - 1107
JO - Science
JF - Science
IS - 6007
ER -
