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

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.