c 语言英文参考文献,Humanized c-Myc Mouse 英文参考文献.doc

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