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Publication : PiggyBac transposon mutagenesis: a tool for cancer gene discovery in mice.

First Author  Rad R Year  2010
Journal  Science Volume  330
Issue  6007 Pages  1104-7
PubMed ID  20947725 Mgi Jnum  J:166063
Mgi Id  MGI:4839668 Doi  10.1126/science.1193004
Citation  Rad R, et al. (2010) PiggyBac transposon mutagenesis: a tool for cancer gene discovery in mice. Science 330(6007):1104-7
abstractText  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.
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