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Plasma cell tumour progression in iMyc Eµ gene‐insertion mice
Author(s) -
Kim JS,
Han SS,
Park SS,
McNeil N,
Janz S
Publication year - 2006
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.1940
Subject(s) - biology , microbiology and biotechnology , immunoglobulin heavy chain , chromosomal translocation , antibody , immunoglobulin gene , transgene , gene , allelic exclusion , plasmacytoma , complementary dna , plasma cell , gene targeting , immunoglobulin light chain , locus (genetics) , genetically modified mouse , cancer research , t cell , genetics , immunology , immune system , multiple myeloma , t cell receptor
The authors have recently reported that gene‐targeted iMyc Eµ mice that carry a His 6 ‐tagged mouse Myc cDNA, Myc His , just 5′ of the immunoglobulin heavy‐chain enhancer, Eµ, are prone to ‘spontaneous’ neoplasms of the B‐lymphocyte lineage. The present study has used histological, immunohistochemical, and molecular genetic methods to investigate a subset of these neoplasms referred to as extraosseous plasmacytomas (PCTs). It is shown that 20.8% (20/96) of tumour‐bearing iMyc Eµ mice on a mixed genetic background of segregating C57BL/6 and 129/SvJ alleles develop PCT by 500 days. The Myc His ‐induced PCTs produced monoclonal immunoglobulin and developed in the gut‐associated lymphoid tissue (GALT), particularly the mesenteric node and Peyer's patches. The PCTs overexpressed Myc His , at the expense of normal Myc , and exhibited gene expression changes on cDNA macroarrays that were consistent with Myc His ‐driven neoplasia. Surprisingly, in one of three PCT‐derived cell lines, Myc His was ‘replaced’ by a naturally occurring T(12;15) translocation, which changed the mode of Myc deregulation from gene insertion ( Myc His transgene) to chromosomal translocation (juxtaposition of normal Myc to the immunoglobulin heavy‐chain locus Igh ). These findings provide evidence that recreation of the mouse PCT‐associated T(12;15)( Igh E µ ‐Myc ) translocation by gene insertion in mice results in the predictable development of PCTs in approximately one‐fifth of the tumour‐bearing mice. Myc His ‐driven PCTs recapitulate aspects of human plasma cell neoplasms, for which relatively few models exist in mice. For example, PCT development in the iMyc Eµ mice may provide a good system to study the mechanism by which human MYC facilitates the progression of plasma cell myeloma (multiple myeloma) in humans. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.