Humanized c-Myc Mouse 英文参考文献
Humanizedc-MycMouse
FrankM.Lehmann1,SamanthaFeicht2,FlorianHelm3,AnnaMaurberger4,CamillaLadinig1,
UrsulaZimber-Strobl2,RalfKu¨hn5,JosefMautner6,ArminGerbitz4,GeorgW.Bornkamm1*
1Institute of Clinical Molecular Biology and Tumor Genetics, Helmholtz Center Munich, Munich, Germany, 2Department of Gene Vectors, Helmholtz Center Munich,
Munich, Germany, 3Department of Immunology, Charite′ Berlin, Berlin, Germany, 4Department of Hematology/Oncology, University of Erlangen, Erlangen, Germany,
5Institute of Developmental Genetics, Helmholtz Center Munich, Neuherberg, Germany, 6Department of Pediatrics, Technical University (TU) Munich and Clinical
CooperationGroupPediatricTumorImmunology,TUMunichandHelmholtzCenterMunich,Munich,Germany
Abstract
Background: Agiventumorisusuallydependentontheoncogenethatisactivatedintherespectivetumorentity.This
phenomenoncalledoncogeneaddictionprovidestherationaleforattemptstotargetoncogeneproductsinatherapeutic
manner,beitbysmallmolecules,bysmallinterferingRNAs(siRNA)orbyantigen-specificTcells.Astheproto-oncogene
product is required also forthefunction ofnormal cells, this raisesthequestion whetherthere is atherapeuticwindow
between the adverse effects of specific inhibitors or T cells to normal tissue that may limit their application, and their
beneficialtumor-specifictherapeuticaction.Toaddressthiscrucialquestion,suitablemousestrainsneedtobedeveloped,
thatenableexpressionofthehumanproto-oncogenenotonlyintumorbutalsoinnormalcells.Theaimofthisworkisto
providesuchamousestrainforthehumanproto-oncogeneproductc-MYC.
PrincipalFindings:WegeneratedC57BL/6-derivedembryonicstemcellsthataretransgenicforahumanizedc-Mycgene
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
endogenousmurinec-Mycgene,homozygousmiceshowanormalphenotypeindicatingthathumanc-MYCcanreplaceits
murin