Genetic reporter system for oncogenic Igh-Myc translocations in mice. Oncogene 2010 Jul 15;29(28):4113-20
Date
05/11/2010Pubmed ID
20453890Pubmed Central ID
PMC3108853DOI
10.1038/onc.2010.150Scopus ID
2-s2.0-77954757627 (requires institutional sign-in at Scopus site) 2 CitationsAbstract
The Myc-deregulating chromosomal T(12;15)(Igh-Myc) translocation, the hallmark mutation of inflammation- and interleukin 6-dependent mouse plasmacytoma (PCT), is the premier model of cancer-associated chromosomal translocations because it is the only translocation in mice that occurs spontaneously (B lymphocyte lineage) and with predictably high incidence (approximately 85% of PCT), and has a direct counterpart in humans: Burkitt lymphoma t(8;14)(q24;q32) translocation. Here, we report on the development of a genetic system for the detection of T(12;15)(Igh-Myc) translocations in plasma cells of a mouse strain in which an enhanced green fluorescent protein (GFP)-encoding reporter gene has been targeted to Myc. Four of the PCTs that developed in the newly generated translocation reporter mice, designated iGFP(5'Myc), expressed GFP consequent to naturally occurring T(12;15) translocation. GFP expression did not interfere with tumor development or the deregulation of Myc on derivative 12 of translocation, der (12), because the reporter gene was allocated to the reciprocal product of translocation, der (15). Although the described reporter gene approach requires refinement before T(12;15) translocations can be quantitatively detected in vivo, including in B lymphocyte lineage cells that have not yet completed malignant transformation, our findings provide proof of principle that reporter gene tagging of oncogenes in gene-targeted mice can be used to elucidate unresolved questions on the occurrence, distribution and trafficking of cells that have acquired cancer-causing chromosomal translocations of great relevance for humans.
Author List
Takizawa M, Kim JS, Tessarollo L, McNeil N, Waldschmidt TJ, Casellas R, Ried T, Janz SAuthor
Siegfried Janz MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsGenes, Reporter
Genes, myc
Green Fluorescent Proteins
Immunoglobulin Heavy Chains
In Situ Hybridization, Fluorescence
Mice
Oncogenes
Polymerase Chain Reaction
Translocation, Genetic