This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Palomo, C. Articles by Brüggemann, M. Search for Related Content PubMed PubMed Citation Articles by Palomo, C. Articles by Brüggemann, M.

B-Cell Tumorigenesis in Mice Carrying a Yeast Artificial Chromosome-based Immunoglobulin Heavy/c-myc Translocus Is Independent of the Heavy Chain Intron Enhancer (Eµ)¹

Laboratory of Developmental Immunology, The Babraham Institute, Babraham, Cambridge CB2 4AT, United Kingdom

We have used YAC (yeast artificial chromosome) technology to create large translocation regions where the c-myc proto-oncogene is coupled to the core region of the human immunoglobulin heavy chain (IgH) locus (from VH2-5 through to C). Chimeric mice were obtained from embryonic stem cells carrying a single copy of the 240-kb IgH/c-myc translocation region. B-cell tumorigenesis occurs in the translocus mice, even when the entire Eµ intron enhancer region between the joining segments and switch µ is deleted. This demonstrates that as yet unidentified regulatory elements in the IgH locus, independent from the known enhancers, are sufficient to cause B-cell specific activation of c-myc after translocation. The phenotype of tumors from IgH/c-myc YAC transgenic mice with or without Eµ (B220⁺, IgM⁺/IgD⁺) is reminiscent of Burkitt’s lymphoma. A rapidly expanding abnormal B-cell population is present at birth and accumulates in bone marrow, periphery, and spleen, well before discrete tumor establishment. Molecular analysis identified a clonal origin, with rearrangement of one mouse heavy chain allele retained in tumor cells from different sites, whereas subsequent rearrangements of heavy or light chain loci can be diverse. These mice routinely develop mature B-cell tumors early in life and may provide an invaluable resource of a B-cell lymphoma model.

This article has been cited by other articles:

				S. E. Khuda, W. M. Loo, S. Janz, B. Van Ness, and L. D. Erickson Deregulation of c-Myc Confers Distinct Survival Requirements for Memory B Cells, Plasma Cells, and Their Progenitors J. Immunol., December 1, 2008; 181(11): 7537 - 7549. [Abstract] [Full Text] [PDF]

				V. Truffinet, E. Pinaud, N. Cogne, B. Petit, L. Guglielmi, M. Cogne, and Y. Denizot The 3' IgH Locus Control Region Is Sufficient to Deregulate a c-myc Transgene and Promote Mature B Cell Malignancies with a Predominant Burkitt-Like Phenotype J. Immunol., November 1, 2007; 179(9): 6033 - 6042. [Abstract] [Full Text] [PDF]

				S. S. Park, A. L. Shaffer, J. S. Kim, W. duBois, M. Potter, L. M. Staudt, and S. Janz Insertion of Myc into Igh Accelerates Peritoneal Plasmacytomas in Mice Cancer Res., September 1, 2005; 65(17): 7644 - 7652. [Abstract] [Full Text] [PDF]

				J. Wang and L. M. Boxer Regulatory Elements in the Immunoglobulin Heavy Chain Gene 3'-Enhancers Induce c-myc Deregulation and Lymphomagenesis in Murine B Cells J. Biol. Chem., April 1, 2005; 280(13): 12766 - 12773. [Abstract] [Full Text] [PDF]

				S. S. Park, J. S. Kim, L. Tessarollo, J. D. Owens, L. Peng, S. S. Han, S. Tae Chung, T. A. Torrey, W. C. Cheung, R. D. Polakiewicz, et al. Insertion of c-Myc into Igh Induces B-Cell and Plasma-Cell Neoplasms in Mice Cancer Res., February 15, 2005; 65(4): 1306 - 1315. [Abstract] [Full Text] [PDF]

				C. A. Mundt, I. C. Nicholson, X. Zou, A. V. Popov, C. Ayling, and M. Bruggemann Novel Control Motif Cluster in the IgH {{delta}}-{{gamma}}3 Interval Exhibits B Cell-Specific Enhancer Function in Early Development J. Immunol., March 1, 2001; 166(5): 3315 - 3323. [Abstract] [Full Text] [PDF]

				J. L. Hecht and J. C. Aster Molecular Biology of Burkitt's Lymphoma J. Clin. Oncol., November 1, 2000; 18(21): 3707 - 3721. [Abstract] [Full Text] [PDF]