Genetic reporter system for oncogenic Igh-Myc translocations in mice.
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.
Takizawa
M
M
Laboratory of Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Kim
J S
JS
Tessarollo
L
L
McNeil
N
N
Waldschmidt
T J
TJ
Casellas
R
R
Ried
T
T
Janz
S
S
D000818:Animals; D017930:Genes, Reporter; D016259:Genes, myc; D049452:Green Fluorescent Proteins / Q000235:genetics; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D009857:Oncogenes; D016133:Polymerase Chain Reaction; D014178:Translocation, Genetic
D007143:Immunoglobulin Heavy Chains; D049452:Green Fluorescent Proteins
Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13588-93
9391070
Oncogene. 2001 Sep 10;20(40):5580-94
11607811
Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):232-5
1729694
Oncogene. 2003 May 8;22(18):2842-50
12743607
Proc Natl Acad Sci U S A. 2009 Feb 24;106(8):2717-22
19196992
Nature. 2000 Mar 30;404(6777):510-4
10761921
Genes Dev. 2003 May 1;17(9):1071-7
12730130
Nature. 2009 Jul 9;460(7252):231-6
19587764
Semin Immunol. 2005 Dec;17(6):431-41
16216522
Leukemia. 2000 May;14(5):909-21
10803525
J Exp Med. 1997 Sep 15;186(6):921-9
9294146
Nat Rev Cancer. 2007 Apr;7(4):233-45
17361217
Nature. 2009 Dec 10;462(7274):803-7
20010689
Cytometry A. 2007 Aug;71(8):542-9
17598185
Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7361-5
8346257
Curr Top Microbiol Immunol. 1997;224:251-5
9308248
Cell. 2004 Aug 20;118(4):431-8
15315756
Proc Natl Acad Sci U S A. 1982 Dec;79(24):7824-7
6961453
Genes Dev. 2001 Aug 15;15(16):2023-30
11511533
Cancer Res. 2003 Dec 15;63(24):8656-63
14695177
DNA Repair (Amst). 2006 Sep 8;5(9-10):1213-24
16815105
Cell. 2008 Dec 12;135(6):1028-38
19070574
Cell. 2000 Sep 1;102(5):553-63
11007474
Cancer Res. 1996 Jan 15;56(2):419-23
8542601
Mol Cell. 2006 Jan 20;21(2):201-14
16427010
Nature. 1969 Jun 7;222(5197):994-5
5789334
Leukemia. 2000 Jun;14(6):1127-35
10865979
Blood. 2000 Aug 1;96(3):808-22
10910891
Blood. 1997 Jan 1;89(1):291-6
8978304
Proc Natl Acad Sci U S A. 2009 Feb 17;106(7):2265-70
19174520
Oncogene. 1997 Nov 6;15(19):2369-77
9393881