IgH enhancer-mediated deregulation of N-myc gene expression in transgenic mice: generation of lymphoid neoplasias that lack c-myc expression

EMBO J. 1989 Apr;8(4):1121-8.

Abstract

We have generated transgenic mouse lines that carry one of three different constructs in which the murine N-myc gene is expressed under the control of the immunoglobulin heavy chain transcriptional enhancer element (E mu-N-myc genes). High-level expression of the E mu-N-myc transgenes occurred in lymphoid tissues; correspondingly, many of these E mu-N-myc lines reproducibly developed pre-B- and B-lymphoid malignancies. The E mu-N-myc transgene also appeared to participate in the generation of a T cell malignancy that developed in one E mu-N-myc mouse. These tumors and cell lines adapted from them expressed exceptionally high levels of the E mu-N-myc transgene; the levels were comparable to those observed in human neuroblastomas with highly amplified N-myc genes. In contrast, all of the E mu-N-myc cell lines had exceptionally low or undetectable levels of the c-myc RNA sequences, consistent with the possibility that high-level N-myc expression can participate in the negative 'cross-regulation' of c-myc gene expression. Our findings demonstrate that deregulated expression of the N-myc gene has potent oncogenic potential within the B-lymphoid lineage despite the fact that the N-myc gene has never been implicated in naturally occurring B-lymphoid malignancies. Our results also are discussed in the context of differential myc gene activity in normal and transformed cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology
  • Cell Differentiation
  • Enhancer Elements, Genetic
  • Female
  • Gene Expression Regulation
  • Gene Rearrangement
  • Genes, Immunoglobulin*
  • Immunoglobulin Heavy Chains / genetics
  • Lymphoma / genetics*
  • Male
  • Mice
  • Mice, Transgenic
  • Oncogenes*

Substances

  • Immunoglobulin Heavy Chains