title: Humanized c-Myc mouse.
abstract: 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.
  
  
  RESULTS
  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.
authors.affiliation: Institute of Clinical Molecular Biology and Tumor Genetics, Helmholtz Center Munich, Munich, Germany.
authors.forename: Frank M
authors.initials: FM
authors.lastname: Lehmann
authors.forename: Samantha
authors.initials: S
authors.lastname: Feicht
authors.forename: Florian
authors.initials: F
authors.lastname: Helm
authors.forename: Anna
authors.initials: A
authors.lastname: Maurberger
authors.forename: Camilla
authors.initials: C
authors.lastname: Ladinig
authors.forename: Ursula
authors.initials: U
authors.lastname: Zimber-Strobl
authors.forename: Ralf
authors.initials: R
authors.lastname: Kühn
authors.forename: Josef
authors.initials: J
authors.lastname: Mautner
authors.forename: Armin
authors.initials: A
authors.lastname: Gerbitz
authors.forename: Georg W
authors.initials: GW
authors.lastname: Bornkamm
mesh_terms: D000818:Animals; D015139:Blotting, Southern; D053595:Embryonic Stem Cells; D005434:Flow Cytometry; D016259:Genes, myc; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010641:Phenotype; D016133:Polymerase Chain Reaction; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc