PiggyBac transposon mutagenesis: a tool for cancer gene discovery in mice.
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. To maximize 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.
Wellcome Trust Sanger Institute, Genome Campus, Hinxton-Cambridge CB10 1SA, UK.
Roland
R
Rad
Lena
L
Rad
Wei
W
Wang
Juan
J
Cadinanos
George
G
Vassiliou
Stephen
S
Rice
Lia S
LS
Campos
Kosuke
K
Yusa
Ruby
R
Banerjee
Meng Amy
MA
Li
Jorge
J
de la Rosa
Alexander
A
Strong
Dong
D
Lu
Peter
P
Ellis
Nathalie
N
Conte
Fang Tang
FT
Yang
Pentao
P
Liu
Allan
A
Bradley
D000818:Animals; D004251:DNA Transposable Elements; D052138:Genes, Neoplasm; D005820:Genetic Testing / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016254:Mutagenesis, Insertional; D009369:Neoplasms / Q000235:genetics; D009857:Oncogenes; D011401:Promoter Regions, Genetic
D004251:DNA Transposable Elements