BACKGROUND: A given tumor is usually dependent on the oncogene that is activated 
in the respective tumor entity. This phenomenon called oncogene addiction 
provides the rationale for attempts to target oncogene products in a therapeutic 
manner, be it by small molecules, by small interfering RNAs (siRNA) or by 
antigen-specific T cells. As the proto-oncogene product is required also for the 
function of normal cells, this raises the question whether there is a 
therapeutic window between the adverse effects of specific inhibitors or T cells 
to normal tissue that may limit their application, and their beneficial 
tumor-specific therapeutic action. To address this crucial question, suitable 
mouse strains need to be developed, that enable expression of the human 
proto-oncogene not only in tumor but also in normal cells. The aim of this work 
is to provide such a mouse strain for the human proto-oncogene product c-MYC.
PRINCIPAL FINDINGS: We generated C57BL/6-derived embryonic stem cells that are 
transgenic for a humanized c-Myc gene and established a mouse strain (hc-Myc) 
that expresses human c-MYC instead of the murine ortholog. These transgenic 
animals harbor the humanized c-Myc gene integrated into the endogenous murine 
c-Myc locus. Despite the lack of the endogenous murine c-Myc gene, homozygous 
mice show a normal phenotype indicating that human c-MYC can replace its murine 
ortholog.
CONCLUSIONS: The newly established hc-Myc mouse strain provides a model system 
to study in detail the adverse effects of therapies that target the human c-MYC 
protein. To mimic the clinical situation, hc-Myc mice may be cross-bred to mice 
that develop tumors due to overexpression of human c-MYC. With these double 
transgenic mice it will be possible to study simultaneously the therapeutic 
efficiency and adverse side effects of MYC-specific therapies in the same mouse.