Dynamic regulation of c-Myc proto-oncogene expression during lymphocyte development revealed by a GFP-c-Myc knock-in mouse

Eur J Immunol. 2008 Feb;38(2):342-9. doi: 10.1002/eji.200737972.

Abstract

c-Myc induces widely varying cellular effects, including cell proliferation and cell death. These different cellular effects are determined, in part, by c-Myc protein expression levels, which are regulated through several transcriptional and post-transcriptional pathways. c-Myc transcripts can be detected in cells at all stages of B and T lymphocyte development. However, little is known about c-Myc protein expression, and how it varies, in developing lymphocytes. Here mice have been generated in which the endogenous c-Myc locus has been modified (c-Myc(G)) so that it encodes a GFP-c-Myc fusion protein. c-Myc(G/G) mice are viable, appear normal and exhibit grossly normal lymphocyte development. Flow cytometric analyses revealed significant heterogeneity in c-Myc protein expression levels in developing c-Myc(G/G) B and T lymphocytes. GFP-c-Myc expression levels were highest in proliferating lymphocytes, suggesting that c-Myc up-regulation is important for promoting lymphocyte cell division, and demonstrating that GFP-c-Myc expression is a marker of proliferating lymphocytes in vivo.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics*
  • Cell Proliferation
  • Gene Expression Regulation / immunology*
  • Green Fluorescent Proteins / biosynthesis
  • Green Fluorescent Proteins / genetics*
  • Hydrozoa / genetics
  • Lymphocyte Activation / genetics
  • Lymphocyte Subsets / cytology
  • Lymphocyte Subsets / immunology
  • Lymphocyte Subsets / metabolism*
  • Mice
  • Mice, Transgenic
  • Oncogene Proteins, Fusion / biosynthesis
  • Oncogene Proteins, Fusion / genetics*
  • Proto-Oncogene Proteins c-myc / biosynthesis
  • Proto-Oncogene Proteins c-myc / genetics*

Substances

  • Oncogene Proteins, Fusion
  • Proto-Oncogene Proteins c-myc
  • green fluorescent protein, Aequorea victoria
  • Green Fluorescent Proteins