1. Swiss Institute for Experimental Cancer Research (ISREC), Ch. des Boveresses 155, CH-1066 Epalinges, Switzerland
2. The G. W. Hooper Foundation and Department of Microbiology and Immunology, University of California at San Francisco (UCSF), San Francisco, California 94143-0552, USA
3. Department of Anatomy and Program in Developmental Biology UCSF, San Francisco, California 94143-0452, USA

Correspondence to: Andreas Trumpp^1,2 Correspondence and requests for materials should be addressed to A.T. (e-mail: Email: Andreas.Trumpp@isrec.unil.ch).

Abstract

Overexpression of the proto-oncogene c-myc has been implicated in the genesis of diverse human tumours. c-Myc seems to regulate diverse biological processes, but its role in tumorigenesis and normal physiology remains enigmatic¹. Here we report the generation of an allelic series of mice in which c-myc expression is incrementally reduced to zero. Fibroblasts from these mice show reduced proliferation and after complete loss of c-Myc function they exit the cell cycle. We show that Myc activity is not needed for cellular growth but does determine the percentage of activated T cells that re-enter the cell cycle. In vivo, reduction of c-Myc levels results in reduced body mass owing to multiorgan hypoplasia, in contrast to Drosophila dmyc mutants, which are smaller as a result of hypotrophy². We find that dmyc substitutes for c-myc in fibroblasts, indicating they have similar biological activities. This suggests there may be fundamental differences in the mechanisms by which mammals and insects control body size. We propose that in mammals c-Myc controls the decision to divide or not to divide and thereby functions as a crucial mediator of signals that determine organ and body size.