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

doi:10.1073/pnas.0406138101

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

Departments of ^*Pathology, ^‡Health Studies, and ^¶Medicine, Section of Hematology–Oncology, University of Chicago, Chicago, IL 60637; ^§Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115; ^∥Division of Oncology, Stanford University, Stanford, CA 94305; and ^**Department of Internal Medicine, Section of Hematology/Oncology, University of Nebraska, Omaha, NE 68132

Communicated by Janet D. Rowley, University of Chicago Medical Center, Chicago, IL, August 24, 2004 (received for review June 11, 2004)

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.

Footnotes

↵ † To whom correspondence should be addressed. E-mail: beverly.baron{at}uchospitals.edu.
Abbreviations: ENU, N-ethyl-N-nitrosourea; tTA, tetracycline-transactivating protein; β-gal, β-galactosidase; X-gal, 5-bromo-4-chloro-3-indolyl β-d-galactoside; FACS, fluorescence-activated cell sorting.