The human BCL6 transgene promotes the development of lymphomas in the mouse

Beverly W. Baron, John Anastasi, Anthony Montag, Dezheng Huo, Rebecca M. Baron, Theodore Karrison, Michael J. Thirman, Sumit K. Subudhi, Robert K. Chin, Dean W. Felsher, Yang Xin Fu, Timothy W. McKeithan, Joseph M. Baron

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Abstract

BCL6, a gene on chromosome 3, band q27, encodes a zinc finger transcriptional repressor that is needed for germinal center formation and has been implicated in the pathogenesis of some human lymphomas when it is mutated or involved in chromosomal rearrangements. To explore further the mechanisms of action of BCL6 in lymphomagenesis, we developed a transgenic mouse model mimicking a common translocation, the t(3, 14)(q27;q32), in human lymphomas. The transgenic mice develop normally and express the transgenic BCL6 protein constitutively in lymphocytes. A small fraction of the animals develop B and T cell lymphomas after a long latency period, but the incidence is dramatically enhanced following administration of N-ethyl-N-nitrosourea, a carcinogen that induces DNA mutations. The N-ethyl-N-nitrosourea-induced lymphomas spread widely, were exclusively T cell, expressed the BCL6 protein, and occurred only in the transgenic mice. Because BCL6 expression has been reported in a number of T cell tumors as well as in the more commonly occurring B cell lymphomas in humans, our transgenic mice provide a model for the study of human lymphomas.

Original languageEnglish (US)
Pages (from-to)14198-14203
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number39
DOIs
StatePublished - Sep 28 2004

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ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Baron, B. W., Anastasi, J., Montag, A., Huo, D., Baron, R. M., Karrison, T., Thirman, M. J., Subudhi, S. K., Chin, R. K., Felsher, D. W., Fu, Y. X., McKeithan, T. W., & Baron, J. M. (2004). The human BCL6 transgene promotes the development of lymphomas in the mouse. Proceedings of the National Academy of Sciences of the United States of America, 101(39), 14198-14203. https://doi.org/10.1073/pnas.0406138101