Faculty Collaboration Database

Plasma cell tumour progression in iMycEmu gene-insertion mice. J Pathol 2006 May;209(1):44-55

Date

02/17/2006

Pubmed ID

16482495

DOI

10.1002/path.1940

Scopus ID

2-s2.0-33645976496 (requires institutional sign-in at Scopus site)   9 Citations

Abstract

The authors have recently reported that gene-targeted iMyc(Emu) mice that carry a His(6)-tagged mouse Myc cDNA, Myc(His), just 5' of the immunoglobulin heavy-chain enhancer, Emu, 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(Emu) 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(Emu)-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(Emu) 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.

Author List

Kim JS, Han SS, Park SS, McNeil N, Janz S

Author

Siegfried Janz MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Cell Transformation, Neoplastic
Chromosomes, Mammalian
DNA, Complementary
DNA, Neoplasm
Disease Models, Animal
Disease Progression
Gene Expression
Genes, myc
Immunoenzyme Techniques
Mice
Mice, Transgenic
Plasmacytoma
Reverse Transcriptase Polymerase Chain Reaction
Translocation, Genetic