PiggyBac Transposon Mutagenesis: A Tool for Cancer Gene Discovery in Mice

作者：Roland Rad, Lena Rad, Wei Wang, Juan Cadiñanos, George S. Vassiliou, Stephen Rice, Lia S. Campos, Kosuke Yusa, Ruby Banerjee, Meng Amy Li, Jorge de la Rosa, Alexander Strong, Dong Lu, Peter Ellis, Nathalie Conte, Fengtang Yang, Pentao Liu, Allan Bradley · 发表于：Science · 年份：2010 · DOI：10.1126/science.1193004 · 被引用次数：235 · 研究领域：CRISPR and Genetic Engineering、Animal Genetics and Reproduction、RNA Interference and Gene Delivery

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.