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

Abstract

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.

• Authors: Roland Rad, Lena Rad, Wei Wang, Juan Cadinanos, George 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, Fang Tang Yang, Pentao Liu, Allan Bradley
• Journal: Science (New York, N.Y.) (Science) Vol. 330 Issue 6007 Pg. 1104-7 (Nov 19 2010) ISSN: 1095-9203 [Electronic] United States
• PMID: 20947725 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA Transposable Elements

Topics

• Animals
• DNA Transposable Elements
• Genes, Neoplasm
• Genetic Testing (methods)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Mutagenesis, Insertional
• Neoplasms (genetics)
• Oncogenes
• Promoter Regions, Genetic