Humanized c-Myc Mouse

  • 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 strBackground 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.show moreshow less

Download full text files

Export metadata

  • Export Bibtex
  • Export RIS

Additional Services

Share in Twitter Search Google Scholar
Metadaten
Author:Frank M. Lehmann, Samantha Feicht, Florian Helm, Anna Maurberger, Camilla Ladinig, Ursula Zimber-Strobl, Ralf Kühn, Josef Mautner, Armin Gerbitz, Georg W. Bornkamm
URN:urn:nbn:de:bvb:29-opus-37113
Title of the journal / compilation:PLoS ONE 7.7 (2012): 29.10.2012 <http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0042021>
Document Type:Article
Language:English
Date of Publication (online):2012/10/30
Publishing Institution:Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU)
Release Date:2012/10/30
SWD-Keyword:-
Original publication:PLoS ONE 7.7 (2012): 29.10.2012 <http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0042021>
Institutes:Medizinische Fakultät -ohne weitere Spezifikation-
Dewey Decimal Classification:610 Medizin und Gesundheit
Collections:Open Access Artikel ohne Förderung 2012

$Rev: 12793 $